Prospective Study of Complete Remissions Observed With Sunitinib in Patients With Metastatic Renal Cell Carcinoma mRCC)
Conditions: Complete Remission in Renal Cell Carcinoma
Sponsor: Pfizer

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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 2 of 89 
1. TABLE OF CONTENTS 
1. TABLE OF CONTENTS .......................................................................................................2 
2. LIST OF ABBREVIATIONS ................................................................................................5 
3. RESPONSIBLE PARTIES ....................................................................................................6 
3.1. OBJECTIVES ...........................................................................................................8 
3.2. METHODS ................................................................................................................9 
3.2.1. Physician population .....................................................................................9 
3.2.2. Patient population .........................................................................................9 
3.2.3. General study design ...................................................................................10 
3.3. STATISTICAL METHODS ...................................................................................10 
4. AMENDMENTS AND UPDATES .....................................................................................12 
5. MILESTONES .....................................................................................................................13 
6. RATIONALE AND BACKGROUND ................................................................................13 
7. RESEARCH QUESTION AND OBJECTIVES .................................................................16 
8. RESEARCH METHODS ....................................................................................................16 
8.1. Study design ............................................................................................................16 
8.1.1. Type of study ..............................................................................................16 
8.1.2. Study schedule ............................................................................................17 
8.1.3. Obtaining of patient's informed consent .....................................................18 
8.1.4. Data collected in the individual case report form for each patient included 
(Appendix 3) ....................................................................................................18 
8.2. Setting ......................................................................................................................21 
8.2.1. Population of physicians/health care professionals ....................................21 
8.2.2. Patient population .......................................................................................21 
8.2.3. Inclusion criteria .........................................................................................22 
8.2.4. Inclusion and exclusion criteria for Controls ..............................................22 
8.2.5. Detailed logistics ........................................................................................22 
8.3. Variables ..................................................................................................................25 
8.4. Data sources ............................................................................................................25 
8.5. Study size ................................................................................................................25 
8.5.1. Complete justification of study population numbers (physicians/patients) 25 
8.6. Data management ....................................................................................................25 
8.6.1. Processing of questionnaires .......................................................................26 
8.6.2. Compiling of the database ..........................................................................26 
8.6.3. Data entry ....................................................................................................26 
8.6.4. Data checking .............................................................................................26 
8.6.5. Coding.........................................................................................................27 

Protocol A6181209 
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8.6.6. Final quality control ....................................................................................27 
8.6.7. Database freeze ...........................................................................................27 
8.6.8. Data management report .............................................................................27 
8.6.9. Data transfer ................................................................................................27 
8.7. Case report forms (CRFs)/Data collection tools (DCTs)/Electronic data record ....27 
8.7.1. Record retention ..........................................................................................28 
8.8. Data analysis ...........................................................................................................28 
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................29 
9.1. Patient information ..................................................................................................29 
9.2. Patient consent .........................................................................................................29 
9.3. Patient withdrawal ...................................................................................................30 
9.4. Institutional review board (IRB)/Independent ethics committee (IEC) ..................30 
9.4.1. French Board of Physicians (CNOM) ........................................................30 
9.4.2. Data protection French Data Protection Agency "CNIL" ..........................30 
9.4.3. Ethics Committee (EC) and declaration of the blood sample bank ............30 
9.4.4. Informing persons and obtaining their consent ..........................................31 
9.4.5. Ministry of research ....................................................................................31 
9.4.6. ANSM - Agence National de Sécurité du Médicament (The French National 
Agency for Medicines and Health Products Safety) ........................................32 
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................32 
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........38 
12. REFERENCES ..................................................................................................................38 
13. APPENDIX ........................................................................................................................40 
13.1. APENDIX 1. Sae form ..........................................................................................40 
13.2. Appendix 2: National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) .........................................................................................42 
13.3. Appendix 3: Information letter and consent form for patient with mRCC in CR 
with Sunitinib (Case) .................................................................................................43 
13.4. Appendix 4: Patient information leaflet and consent form for patients with mRCC 
selected as controls and treated with Sunitinib ..........................................................46 
13.5. Appendix 5: Case report form for patients with mRCC in complete remission 
(Cases) .......................................................................................................................43 
13.6. Appendix 6: Case report form for patients with mRCC NOT in complete remission 
(Controls) ...................................................................................................................53 
13.7. Appendix 7: Laboratory tests ................................................................................62 
13.8. Appendix 8: Prognostic factors .............................................................................63 
13.9. Appendix 9: RECIST v 1.1 assessment criteria ....................................................64 
13.10. Appendix 10: Centralized reading CT SCANS ...................................................65 

Protocol A6181209 
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13.11. Appendix 11: Methods for collecting and transporting biological samples ........66 
13.12. Appendix 12: Methods for collecting and transporting histological samples .....70 
13.13 
Appendix 13: Sutent – product caracteristics summary ..................................74 
 
 

Protocol A6181209 
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Page 5 of 89 
2. LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
ANSM 
Agence Nationale de sécurité du médicament  (National sécurity medicine agency) 
CCTIRS 
Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans 
le domaine de la Santé (French Advisory Committee for Data Processing in Health 
Research) 
CNIL 
Commission Nationale de l’Informatique et des Libertés (French Data Protection 
Agency) 
CNOM 
Conseil National de l’Ordre des Médecins (French National Board of Physicians) 
CR 
Complete Remission 
CRO 
Contract Research Organization 
EC 
Ethics Committee 
eCRF 
electronic Case Report Form 
HAS 
Haute Autorité de Santé (French Health Authority) 
mRCC 
metastatic Renal Cell Cancer 
MSKCC 
Memorial Sloan-Kettering Cancer Center 
RCC 
Renal Cell Cancer 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SmPC 
Summary of Product Characteristics 
TKI 
Tyrosine Kinase Inhibitor 
VEGF 
Vascular Endothelial Growth Factor 
 

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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 8 of 89 
ABSTRACT 
Complete remission (CR) is a rare event during the treatment of metastatic renal cell carcinoma (mRCC) 
with tyrosine kinase inhibitors (TKIs), but results from two retrospective cohorts show that it occurs in 1 
to 2% of patients treated with Sunitinib. 
This CR with Sunitinib has been described in the different prognostic subgroups and it has also been 
reported in the case of multiple metastases. In addition, a series of reports suggests that significant 
objective responses can be obtained in a subpopulation of patients receiving targeted therapy and that a 
complete residual metastasectomy can be beneficial in carefully screened patients having presented a 
partial response to antiangiogenic treatment. 
The continuation of treatment or its withdrawal in patients presenting CR with Sunitinib is not part of 
standardized treatment. 
Moreover, treatments targeting vascular endothelial growth factor (VEGF) are associated with the onset 
of resistance after a treatment period of 6 to 15 months. The sequential use of these drugs has become 
standard practice. Indeed, activity can be observed with an agent having the same target as, or some 
targets in common with, one of the previous treatments and for which disease progression had been 
observed. This therefore raises questions regarding the mechanism(s) of this resistance and the optimal 
therapeutic approach in this context. This resistance appears to be a potentially reversible mechanism. In 
a retrospective review performed on patients with mRCC treated with Sunitinib, after disease progression 
occurring following previous treatment with Sunitinib and other treatments, the reintroduction of 
Sunitinib was effective and well-tolerated in the majority of cases. 
In patients in CR with targeted treatment only or thanks to the combination of targeted treatment and an 
additional metastasectomy, one series indicates that, in almost half of cases, withdrawal of Sunitinib 
treatment was followed by a recurrence, but that reintroduction of this targeted therapy was effective in 
the majority of cases. 
A better characterization of patients experiencing CR with Sunitinib is therefore required in order to 
provide information to physicians about the treatment approach to adopt in such cases and to encourage 
surgeons to operate on patients with single or minimal residual metastases. 
The analysis of patients experiencing CR must compare these rare cases to the most common situation in 
patients treated with Sunitinib where no complete response is developed. Given the rarity of the event 
studied, the design proposed is that of a case-control study. 
 
3.1. OBJECTIVES 
Primary objective 
To describe the characteristics of patients with mRCC and presenting CR with Sunitinib (Cases) and 
compare them with the characteristics of patients with mRCC and not presenting CR with Sunitinib 
(Controls) in order to identify factors associated with the occurrence of complete remission. 
Secondary objectives: 
• 
To describe the therapeutic treatment methods (discontinuation of treatment or continuation of 
systemic treatment in patients in CR) 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 9 of 89 
 
• 
To investigate and describe various biomarkers in a blood bank of samples drawn during CR with 
Sunitinib in patients in CR (Cases) and at the time of recurrence, if it occurs 
• 
To investigate and describe various biomarkers in a histological specimen collection bank prior to 
initiation of sunitinib in CR (Cases) and non-CR patients treated with sunitinib (controls). 
• 
To compare biomarkers identified in patients in CR (Cases) to those in patients not in CR with 
Sunitinib (Controls). 
 
3.2. METHODS 
3.2.1. Physician population 
This case-control observational study will be conducted by oncologists at around twenty metropolitan 
oncology centers in France. 
3.2.2. Patient population 
40 patients with metastatic renal cell carcinoma in CR with Sunitinib (Cases) and 80 patients with 
metastatic renal cell carcinoma receiving first-line treatment with Sunitinib (Controls) will be included 
in this research and followed for a period of 36 months. 
Inclusion and exclusion criteria for Cases 
Inclusion criteria 
• Adult patients (≥ 18 years) 
• Patients with mRCC confirmed by histological analysis 
• Treated with Sunitinib according to a regimen in the section of the Summary of Product 
Characteristics (SmPC) 
• Presenting a complete remission in the preceding 5 years (according to RECIST v1.1) with 
Sunitinib only or combined with localized treatment (surgery, radiotherapy, cryoablation or 
radiofrequency ablation) 
• Patients of childbearing age using a mandatory method of contraception 
• Affiliated to a social security scheme 
• Informed about the study methods and having given their consent 
 
Exclusion criteria 
• Complete remission occurring in the absence of treatment with Sunitinib 
 
Inclusion and exclusion criteria for Controls 
Inclusion criteria 
• Adult patients (18 years) 
• Life expectancy ≥ 3 months 
• Patients with mRCC confirmed by histological analysis 
• No previous treatment with Sunitinib 
• Patients for whom the indication of Sutent® is retained in compliance with the text in the 
SmPC 
• Platelets  100 x 109/l, hemoglobin > 9 g/dl, neutrophils >1.5 x 109/l 
• Bilirubin < 2 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT)  
2.5 times upper limit of normal or  5 times upper limit of normal in the presence of hepatic 
metastases 
• Patients of childbearing age using a mandatory method of contraception 
• Affiliated to a social security scheme 
• Informed about the study methods and having given their consent 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 10 of 89 
 
Exclusion criteria 
• Previous systemic treatment 
• Patients who are pregnant or breastfeeding 
• Any contraindications to Sunitinib in accordance with the text in the SmPC 
 
 
3.2.3. General study design 
Cross-sectional then longitudinal, comparative, multicenter, prospective, case-control study including 
40 patients with metastatic renal cell carcinoma in CR with Sunitinib (Cases) and 80 patients with 
metastatic renal cell carcinoma with no CR receiving Sunitinib as first-line treatment (Controls). 
Blood samples will be drawn from patients with metastatic renal cell carcinoma in CR with Sunitinib 
(Cases) during screening visit and in the case of disease progression. 
Blood samples will be drawn from patients with metastatic renal cell carcinoma in the absence of CR 
with Sunitinib (Controls) before start of Sunitinib, at 6 months, at 12 months and during disease 
progression. 
Note that a patient in the Control group may move to the Case group if s/he presents a CR during 
follow-up with Sunitinib. 
Duration of inclusions: 4 years  
Follow-up of patients: 3 years 
 
3.3. STATISTICAL METHODS 
The primary objective of the study is to describe the characteristics of patients with mRCC and 
presenting CR with Sunitinib (Cases) and compare them with the characteristics of patients with 
metastatic renal cell carcinoma without CR with Sunitinib in order to identify factors associated with the 
occurrence of complete remission. 
A sample size of N = 40 (Cases) and N = 80 (Controls) will give a statistical power of 80% in revealing: 
• For a continuous variable with a normal distribution, an effect size (Cohen's d) ≥ 0.55; 
• For a dichotomous variable, a difference in frequency between cases and controls corresponding to the 
ORs presented in the table below: 
Frequency in the 
control 
10% 
20% 
30% 
40% 
50% 
60% 
70% 
80% 
90% 
Odds Ratio 
 
 
≥4.33 
 
 
≥3.27 
≤0.19 
or 
≥3.16 
≤0.26 
or 
≥3.12 
≤0.29 
or 
≥3.44 
≤0.32 
or 
≥3.78 
≤0.32 
or 
≥5.29 
≤0.31 
≤0.23 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 11 of 89 
 

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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 13 of 89 
5. MILESTONES 
 
Milestone 
Planned date 
Start of data collection  
Juillet 2014 
End of data collection  
Décembre 2021 
Rapport intermédiaire 
Janvier 2019 
Final study report 
Novembre 2022 
 
6. RATIONALE AND BACKGROUND 
Context 
The incidence of renal carcinoma in France was estimated at 10,125 cases in 2009 1. It represents around 
3% of malignant tumors in adults. In 85% of cases, it is a renal cell carcinoma (RCC). The incidence of 
renal carcinoma has been increasing over the last 30 years; probably related to a greater number of 
incidental diagnoses. It is twice as frequent in men. The average age at diagnosis is around 65 years. The 
number of estimated deaths in 2009 was about 3,830. This number is decreasing, partly associated with 
earlier discovery of these cancers. In fact, worldwide, the relative survival at 5 years is 63% 2. For a 
localized stage (58% of diagnoses), this increases to 90%. Peak mortality occurs between 75 and 85 
years3. 
It is estimated that 10 to 40% of patients diagnosed with renal carcinoma already have a metastatic form 
of the disease. Despite initial curative treatment, 10 to 30% will develop metastases, with an average time 
of 36 months to appearance of metastases. These metastatic forms have a poor prognosis (survival rate at 
2 years of 10% - 20% 4) because of the increased resistance to conventional chemotherapies and to 
radiotherapy. For many years, the treatment of metastatic renal cell carcinoma has been based on 
nephrectomy and adjuvant immunotherapy (interleukin 2, interferon alpha); often toxic and of limited 
efficacy in terms of survival 5. 
Since 2009, the treatment of metastatic renal cell carcinoma remains partially surgical, particularly for 
excision of the primary tumor, but equally for individual metastatic localizations. Outside of these 
indications, the standard treatment is based on antiangiogenic drugs. For patients belonging to the good 
or moderate prognosis group, the choice of first-line treatment, according to ASCO and CCAFU 
(Oncology Committee of the French Urology Association), is Sunitinib, the combination 
Bevacizumab/interferon α or Pazopanib. These targeted therapies have revolutionized the treatment of 
patients with metastases, achieving a significant therapeutic response and an improvement in patients' 
survival rates. However, numerous questions remain as to the methods of using these antiangiogenic 
treatments 5. 
Study rationale 
Complete remission (CR) is a rare event during the treatment of mRCC with tyrosine kinase inhibitors 
(TKIs), but results from two retrospective cohort studies show that it occurs in 1 to 3% of patients treated 
with Sunitinib. (Motzer 2008 6: 1%; Motzer 2009 7: 3%; Heng 2007 8: 2.7%; Albiges ASCO 2010 9: 
1.7%). 
CR with Sunitinib has been described in the different prognostic subgroups as defined by the modified 
classification of Motzer 2002 10 [Memorial Sloan-Kettering Cancer Center (MSKCC) classification] and 
has also been reported in cases with multiple metastases 9. In addition, a series of reports suggests that 
significant objective responses can be obtained in a subpopulation of patients receiving targeted therapy 
and that a complete residual metastasectomy can be beneficial in carefully screened patients having 
presented a partial response to antiangiogenic treatment 8, 9, 12. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 14 of 89 
The continuation of treatment or its withdrawal in patients presenting CR with Sunitinib is not currently 
considered to be standard treatment. 
Moreover, treatments targeting VEGF are associated with the onset of resistance after a treatment period 
of 6 to 15 months. The sequential use of these drugs has become standard practice. Indeed, activity can 
be observed with an agent having the same target as the previous treatment having led to a disease 
progression. This therefore raises questions regarding the mechanism(s) of this resistance and the optimal 
therapeutic approach in this context 13. This resistance appears to be a potentially reversible mechanism. 
A retrospective review was done on patients with mRCC treated with Sunitinib after disease progression 
occurring after prior treatment with Sunitinib and other treatments. The reintroduction of Sunitinib was 
effective and well-tolerated 14. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 15 of 89 
 
Recently, in 36 patients (including 22 on Sunitinib) in CR with targeted therapy only or absence of signs 
of the disease after an additional metastasectomy, Johannsen et al. 15 demonstrated that withdrawal of 
treatment was followed by a recurrence, but that the reintroduction of this targeted therapy was effective. 
A better characterization of patients experiencing CR with Sunitinib is therefore required in order to 
provide information to physicians about the treatment approach to adopt in such cases and to encourage 
surgeons to operate on patients with single or minimal residual metastases. 
Because complete remission is a rare event, one can stipulate that this situation should be a model for 
studying the pathology of mRCC in response to Sunitinib. It should also permit the sensitivity and 
resistance to Sunitinib to be explored. 
Research is also required to identify markers that can facilitate the screening of patients who would be at 
low risk of recurrence after complete remission and could potentially benefit from a discontinuation of 
treatment. 
To this end, it is essential to explore the characteristics of the patient at the time of the complete 
remission compared to those observed at the time of the recurrence, if this occurs, in order to attempt to 
answer the following questions: 
• Is it possible to identify a differential blood marker at the time of the CR compared to the 
recurrence phase? 
• Does one have to distinguish between a CR obtained with medical treatment only and one 
obtained with the combination of "medical treatment + localized treatment" when, during the 
retrospective analysis of a series of cases, the 2 cohorts presented the same time to recurrence? 
• Can we identify serum or histologic biomarkers that are potentially predictive of a recurrence or 
CR? 
• Is there a correlation between biomarkers identified in patients in CR with Sunitinib compared 
to patients not in CR with Sunitinib? 
• 
Does the identification of biomarkers help physicians make the decision to stop or continue 
treatment after obtaining a complete response under sunitinib? 
 
Several biomarkers belonging to different categories, are undergoing investigation because they could 
reflect the emergence of a resistance or sensitivity to the medicinal product: 
• Adhesion molecules (cadherin-6, E-cadherin, MUC1/EMA, ICAM-1, VCAM-1, ELAM- 1, 
KSA) 
• Inducers of immunosuppression (HLA class 1, IL-6, IL-8, IP-10, MIG, MIP1b, B7-H1, B7-H4, 
CD44) 
• Growth factor receptors (VEGFR-3, TGFbR-II, FGFR) 
• Hypoxia-inducible factors (CAIX, CAXII, CXCR-4, HIF-1a, VEGF, IGF-I) 
• Proliferation markers (Ki-67, PCNA, Ag-NORs) 
• Cell cycle regulatory proteins (p53, Bcl-2, PTEN, cyclin A, Akt, p27) 
• Analysis of single nucleotide polymorphisms (SNPs) of VEGF and of VEGFRs 
• Others (VHL, mTOR, ribosomal protein S6, survivin, IMP3, caveolin-1, PCR, vimentin, fascin, 
serum amyloid A, NGAL, IGF-1). 
Some of these biomarkers can be detected in the serum (SDF1a, IL-6, IL-8, bFGF, sICAM1, LDH, 
VEGF, PlGF, soluble VEGF receptors, collagen IV, CPCs, SNPs of VEGF) 16 and will be explored in the 
context of CR, especially IL-8, which has been the most documented 17. 
Other potential biomarkers expressed on the surface of tumor cells or immune cells can be investigated 
by immunohistochemistry such as: 
• The expression of BAP1, SETD2, PBRM1, as well as PD1 or PDL1 
• Potential biomarkers of inflammation and lymphocyte infiltrate 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 16 of 89 
A classification according to the tumor expression profile will be performed (B. Beuselinck et al, CCR, 
2015). 
In addition, we will be able to carry out the sequencing of the most frequently mutated genes (PBRM1, 
BAP1, VHL) 
Because, at present, circulating tumor cells can only be studied in fresh blood, and because this marker 
has not yet been validated as regards mRCC, this investigation will not be possible with our cohort. 
However, circulating free DNA is currently being investigated as a substitute for circulating tumor cells 
in various tumor models (prostate, colon and breast) and we regard it as a good candidate for study in our 
population at the time of CR compared to recurrence, if it occurs. 
Therefore, the aims of this multicenter prospective study on patients with metastatic renal cell carcinoma 
in CR with Sunitinib with or without associated localized treatment and control patients with metastatic 
renal cell carcinoma treated with Sunitinib are: 
 
a) To analyze the characteristics of patients with mRCC in CR with Sunitinib 
b) To assess the possibility of patients in CR to discontinue Sunitinib 
c) To collect a prospective bank of blood samples in order to study blood biomarkers in the 
context of the CR and during recurrence 
d) to collect a bank of histological specimens to study biomarkers before the initiation 
of sunitinib; 
e) To assess the correlation between biomarkers analyzed in patients in CR and patients not 
in CR with Sunitinib 
 
7. RESEARCH QUESTION AND OBJECTIVES 
The objectives of this study are as follows: 
Primary objective 
• To describe the characteristics of patients with mRCC and presenting CR with Sunitinib (Cases) and 
compare them with the characteristics of patients with metastatic renal cell carcinoma without CR 
with Sunitinib in order to identify factors associated with the occurrence of complete remission. 
Secondary objectives 
• To describe the methods of therapeutic treatment (discontinuation of treatment or continuation of 
systemic treatment in patients with CR). 
• To investigate and describe various biomarkers in a blood bank of samples drawn during CR with 
Sunitinib in patients in CR (Cases) and at the time of recurrence, if it occurs 
• To investigate and describe various biomarkers in a bank of histological samples collected during the 
CR with Sunitinib and at the time of the recurrence, if it occurs (FGF, IL-8, VEGF, VEGF SNPs etc.). 
• To compare the biomarkers identified in patients with CR (Cases) to those of without CR with 
Sunitinib during the 36 months of the study (Controls). 
8. RESEARCH METHODS  
8.1. Study design 
8.1.1. Type of study 
It is a cross-sectional then longitudinal, comparative, multicenter, prospective, case-control observational 
study with collection of blood samples. 
In addition to the patient's usual medical treatment, as described in the HAS's long-term diseases guide, 
validated by a multidisciplinary working group 19, the specific monitoring methods provided for in this 
research comprise of: 

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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 18 of 89 
- Recruitment of patients: July 2014 – Until inclusion of all the patient in the study or later in 
December 2018 
- End of follow-up: July 2014 – December 2021 
- Database freeze and initial analysis: February 2022 
- Final report: November 2022 
8.1.3. Obtaining of patient's informed consent 
An informed consent form, accompanied by a patient information leaflet in which the purpose of the 
blood samples collected will be clearly stated, will be signed by each patient before any data collection. 
In addition, it will be mentioned that the histological samples taken at the diagnosis of the patients will be 
collected in order to constitute a bank of samples 
A second informed consent form specific to the genetic analyses will be signed by each patient prior to 
all sampling. 
8.1.4.  Data collected in the individual case report form for each patient included (Appendix 3) 
A) Data relating to the physician 
• 
Surname, first name 
• 
Gender 
• 
Age 
• 
Zip code, Town 
• 
Public or private practice 
• 
Type of contract 
 
B) Screening form (only for cases) 
• 
Visit screening date 
• 
Consentment sign date 
• 
Inclusion and non inclusion criteria 
• 
Demographic data: month and year of birth (MM/AAAA) 
• 
Data relating to the initial treatment of the patient: date of diagnosis of the initial renal cancer, 
date of diagnosis of renal cell carcinoma 
• 
Data relating to the status of the patient in complete remission: Sunitinib start date, number and 
localization of metastatic sites at initiation of Sunitinib 
• 
Blood samples during the screening visit: yes / no sampling and date of collection. If the 
samples are not available during the screening visit, a period of 6 weeks between screening and 
sampling will be allowed. 
• 
Histological samples: date of sampling, type of sample, method of fixation. 
 
C) Data collected at inclusion 
For the cases 
• 
Demographic data: age, gender, height, weight 
• 
Data on the diagnosis of patients with metastatic renal cancer in complete remission: date of 
initial diagnosis of kidney cancer, date of diagnosis of metastatic renal cell carcinoma, 
nephrectomy (Yes / No), date of nephrectomy, type of nephrectomy; fixation method, OMS 
pathological classification, TNM classification 2009, Furhman nuclear grade, presence of 
necrosis, tumor size, presence or absence of a sarcomatoid embolus component  
• 
Data relating to the state of the patient in CR at initiation of Sunitinib: initiation date, location of 
metastases, number of metastatic sites, prognostic classification MSKCC  
• 
Data on complete remission: date of complete remission; obtained by medical treatment alone 
or combined with local treatment, radiological assessment of complete remission, Therapeutic 
strategy after complete remission: continuation or discontinuation of treatment 
For the controls 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 19 of 89 
• 
Data relating to the inclusion and demographic data : consultation date ; demographic data : 
year of birth, age, sex, size, weight 
• 
Data relating to the renal metastatic cancer initial treatment for a patient in complete remission : 
date of initial diagnosis of renal cancer, date of diagnosis of metastatic renal cancer, date of 
intitiation of Sutent, nephretomy (Yes/No), date and nephrectomy type, histology, OMS 
anatomopathologic classification, TNM 2009 classification, Furhman nuclear grad, necrosis 
presence, vascular embolism, blood sample date before initiation od Sutent 
• 
Data relating to a patient state with a mRRC before initiation of sunitinib: blood and 
histological sample (Yes/No) and sample date. If the sample are not available during the 
screening visit, un six week time limit between screening and inclusion visit is authorized 
metastasis localisation, number of metastasis, MSKCC prognostic classification 
 
D) Data collected during follow-up visits 
In this research, patient follow-up will be carried out over a period of 3 years, in accordance with the 
normal treatment procedures for this disease (visits every 2 to 3 months as per the expert opinion reported 
in the long-term diseases guide of the HAS). 
For the cases 
During the visit to diagnose possible disease progression, the following data will be recorded in the 
case report form: 
• 
Date of the visit, 
• 
Date of progression, progression type, for a known  metastatic site ou a new metastatic site 
• 
Localization and number of metastatic sites 
• 
Blood sample date 
• 
treatment administered during progression 
 
During the annual visit, following data will be recorded in the case report form: 
• 
disease evolution 
• 
treatment modification (temporary stop, definitive stop), 
• 
No sample to be made 
 
During the end of research visit (36 months after the inclusion visit), the following data will be recorded 
in the case report form : 
• 
36 months visit : Yes/No ; Date of the visit, treatment best answer post progression, duration of 
administration, local treatment associated 
• 
Last news : premature stop of the study ; date of latest news ; persistant remission complete 
since visit of inclusion ; complete remission after treatment of progression post RC ; progression 
of cancer ; number of subsequent line of treatment after Sutent 
• 
Deaths (YES / NO), date of death 
 
For the controls 
During the follow-up visits at 6 and at 12 months, the following data will be recorded in the case report 
form : 
• 
Data relating to a patient state with a mRRC at 6 and 12 months of treatment with Sutent : date 
of the visit, clinic evaluation with RECIST criteria, : response to the treatment, stability of the 
disease or progression, date of the progression, type of progression ; metastatic sites ; 
localization and number of metastatic sites ; blood sample and date of sample.  
During the visit of progression: the following data will be recorded in the case report form : 
• 
Data relating to a patient with a mRRC with a progression : date of the visit, date of 
progression, to a known metastatic site, new metastatic site, metastatic sites : localization and 
number of metastatic sites ; blood sample and sample date.  

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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 22 of 89 
. Inclusion and exclusion criteria for Cases: 
8.2.3. Inclusion criteria 
• 
Adult patients (≥ 18 years) 
• 
Patients with mRCC confirmed by histological analysis 
• 
Treated with Sunitinib according to a regimen in the text of the SmPC 
• 
Presenting a complete remission in the preceding 5 years (according to RECIST v1.1) with 
Sunitinib only or combined with localized treatment (surgery, radiotherapy, cryoablation or 
radiofrequency ablation) 
• 
Patients of childbearing age using a mandatory method of contraception 
• 
Affiliated to a social security scheme 
• 
Informed about the study methods and having given their consent 
 
Exclusion criteria 
• 
Complete remission occurring in the absence of treatment with Sunitinib 
8.2.4.  Inclusion and exclusion criteria for Controls 
Inclusion criteria 
• 
Adult patients (18 years) 
• 
Life expectancy ≥ 3 months 
• 
Patients with mRCC confirmed by histological analysis 
• 
No previous treatment with Sunitinib 
• 
Patients for whom the indication of Sutent® is retained in compliance with the text in the 
SmPC 
• 
Platelets  100 x 109/l, hemoglobin > 9 g/dl, neutrophils >1.5 x 109/l 
• 
Bilirubin < 2 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT)  2.5 times 
upper limit of normal or  5 times upper limit of normal in the presence of hepatic metastases 
• 
Patients of childbearing age must use a method of contraception 
• 
Affiliated to a social security scheme 
• 
Informed about the study methods and having given their consent 
 
Exclusion criteria 
• 
Previous systemic treatment 
• 
Patients who are pregnant or breastfeeding 
• 
Any contraindications to Sunitinib in accordance with the text in the SmPC 
8.2.5. Detailed logistics 
8.2.5.1.  Initiation of the study 
The oncologists who agreed to participate in the study during the feasibility study will receive a letter 
containing: 
- 
A covering letter with a reply slip to be returned to Pfizer's logistics center 
- 
A study synopsis 
- 
The participating physicians' contracts, one copy of which should be returned to Pfizer's logistics 
center 
- 
A pre-paid envelope 
Physicians who did not respond to the emails will be contacted again by telephone fifteen (15) days later 
until the desired number of participating physicians has been reached. 
Once the contract has been signed and returned to Pfizer's logistics center, it will be validated by Pfizer. 
The physician will be contacted by mail to know if he want a website monitoring visit for his center. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 23 of 89 
If the physician want a website monitoring visit so this one will be program with his disponibilities. The 
member of personal Pfizer of each department will be present : 
- 
Post AMM study gestion 
- 
Medical oncology 
- 
Pharmacovigilance 
The physician will receive the study website address and his access code. The physician will found on the 
website the following documents 
- 
CCTIRS opinion 
- 
EC opinion 
- 
CNOM opinion 
- 
CNIL opinion 
- 
Authorization from the Ministry of Research 
- 
The study protocol and protocol amendment 
- 
The memorandum to physicians 
- 
The serious adverse events (SAE) declaration form (Appendix 1) 
In addition, data relating to the physician (year of registration, year of doctoral thesis, town where 
practicing etc.) can be uploaded to the website as well as the anonymized data regarding the patients. 
Also, the physician receive by mail : 
- 
A file containing all documents in the paper version of study (protocol, regulatory 
agreements, etc ...)  
- 
briefings / patient consent  
- 
CD / ROMs and pre postage for mailing envelopes at IGR  
- 
aliquots pellets and pre-labeled and forms for the transport of blood samples  
- 
envelopes sufficient to return the document 
- 
Each physician investigator will be a single number (0001 to 00XX). 
 
The physicians will be presented with a hotline number as well as an email address where they can ask 
questions about the conducting of the study. 
8.2.5.2.  Screening of patients 
Before any gathering of personal data, the physician will invite the patient to participate in this research 
and will inform him/her about: 
- 
The objective, the nature of the constraints 
- 
The computer processing of his/her data that will be collected during this research and will also 
specify his/her rights of access, opposition and rectification of his/her data 
- 
The storage of blood samples for scientific purposes at the end of the research 
In addition, during this visit (screening visit), the physician will check the eligibility criteria. 
Finally, an information leaflet summarizing these different points will be handed to the patient. 
If the patient with metastatic renal cell carcinoma in CR with Sunitinib (Cases) consents to participate in 
the research, the physician should during the screening visit:  
• Obtain his/her express written consent (Appendix 2) 
• Complete the screening form and send it, along with the 2 CT scan burnet on 2 CD-ROM, to the 
IGR. 
• Complete the inclusion questionnaire 
• Draw 10 ml of blood into 2 EDTA tubes of 5 ml each and send the sample after centrifugation 
to the IGR 
• Collection of a block or in the absence of 15 white slides from a histological sample  
If the patient in CR presents disease progression during the 3 years of follow-up: 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 24 of 89 
• Complete the disease progression questionnaire 
• Draw 10 ml of blood into 2 EDTA tubes of 5 ml each and send the sample after centrifugation 
to the IGR 
• Collection of a block or in the absence of 15 white slides from a histological sample 
 
If the patient with metastatic renal cell carcinoma without CR with Sunitinib (Controls) consents to 
participate in the research, the physician should:  
• Obtain his/her express written consent (Appendix 3) 
• Complete the inclusion questionnaire 
• Draw 10 ml of blood into 2 EDTA tubes of 5 ml each before starting Sunitinib, at 6 months, at 
12 months and during disease progression and send the sample after centrifugation to the IGR. 
 
 Receipt and collection of case report forms 
The Pfizer project managers will ensure monitoring of incomplete or inconsistent data (checking of 
inconsistencies, non-responses and omissions) and will be in permanent contact with the physicians. 
During the patient screening phase, and based on the number of physicians (no patient enrolled), the 
project managers will be required to contact these physicians again and remind them about the study 
deadlines. 
8.2.5.3. End of study 
The project manager will inform the physician about the end of patient enrollment and will remind 
him/her again regarding possible missing documents required for remuneration or inconsistencies in the 
gathered data identified during data management. 
8.2.5.4. Roles of those conducting the study 
Via its project managers, the logistics center will ensure the telemonitoring as well as the centralized e-
monitoring of the participating physicians (use of Pfizer's study management database and the dedicated 
study website). 
The company responsible for the biometrics will ensure the configuration of the eCRF, the issuing of 
correction requests, the writing of the statistical analysis plan, the statistical report and the clinical report 
of the study. 
The oncologists must ensure the screening of patients and the gathering of case report form data while 
observing the research protocol as well as the contract. 
8.2.5.5. Logistical monitoring 
The monitoring of the participating physicians will be done by a team of project managers specially 
trained for the study. This monitoring may be done in various manners: telephone call, email, specific 
letter and newsletter. 
These contacts will be advantageous because they will promote the involvement of and the quality of the 
work done by the participating physicians. As far as possible, everyone will be monitored by the same 
project manager, from their recruitment to close-out of the study. 
The project managers will ensure monitoring of incomplete or inconsistent data (checking of 
inconsistencies, non-responses and omissions) and will be in permanent contact with the participating 
physicians. During the patient screening phase and depending on the number of inactive participating 
physicians (no patient screened), the project managers may need to send them reminders. 
In addition, a study-specific toll-free number will be provided for use by the participating physicians in 
order to be able to respond to their questions throughout the study. 
In terms of traceability, all of the "incoming" and "outgoing" (screening call, reminder call etc.) calls to 
this toll-free number will be the subject of a written report (date, reason for call, action required etc.) and 
will be recorded in dashboards. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 25 of 89 
 
8.3. Variables 
 
8.4. Data sources  
Inclusion data 
Descriptive statistics will be used to describe the patient population and the therapeutic treatment 
methods. More specifically, this will consist of the demographic profile of the patients, the associated 
diseases and concomitant treatments, data relating to the initial treatment of the cancer, data relating to 
disease progression, the kind of localized treatment received that led to the complete remission, data 
relating to the patient's health status and to the status of the disease at the start of Sunitinib, data relating 
to the complete remission and the treatment strategy after the complete remission. 
End-of-study visit data 
The number of deaths and the status of patients will be analyzed.  
Supplementary data 
Blood samples will be drawn from patients with metastatic renal cell carcinoma in CR with Sunitinib 
(Cases) during complete remission and in the case of disease progression. 
Blood samples will be drawn from patients with metastatic renal cell carcinoma in the absence of CR 
with Sunitinib (Controls) before start of Sunitinib, at 6 months, at 12 months and during disease 
progression. 
8.5. Study size 
The primary objective of the study is: 
To describe the characteristics of patients with metastatic renal cell carcinoma and presenting CR with 
Sunitinib (Cases) and to compare them with the characteristics of patients with mRCC and not presenting 
CR with Sunitinib (Controls) in order to identify factors associated with the occurrence of complete 
remission. 
8.5.1. Complete justification of study population numbers (physicians/patients) 
A sample size of N = 40 (Cases) and N = 80 (Controls) will give a statistical power of 80% in revealing: 
• For a continuous variable with a normal distribution, an effect size (Cohen's d) ≥ 0.55; 
• For a dichotomous variable, a difference in frequency between cases and controls corresponding to the 
ORs presented in the table below: 
Frequency in the 
control 
10% 
20% 
30% 
40% 
50% 
60% 
70% 
80% 
90% 
Odds Ratio 
 
 
≥4.33 
 
 
≥3.27 
≤0.19 
or 
≥3.16 
≤0.26 
or 
≥3.12 
≤0.29 
or 
≥3.44 
≤0.32 
or 
≥3.78 
≤0.32 
or 
≥5.29 
≤0.31 
≤0.23 
8.6. Data management  
The contract research organization in charge of data management will process the research data for all 
patients. 
The data may exist in paper and/or electronic format. 
All of the data management operations will be performed in accordance with Pfizer's requirements and 
with the CRO's standard operating procedures. 
A data management plan, defining and describing all of the biometric activities, will be developed by the 
CRO and submitted to Pfizer for validation 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 26 of 89 
 
8.6.1. Processing of questionnaires 
After validation of the physician's financial agreement by the logistics center, s/he will receive 
personalized access to the dedicated study website. This access will comprise the URL as well as the 
passwords required for secure access. Following their receipt, the participating physician will have access 
to the study. S/he will have the option to either save his/her data in order to be able to modify his/her 
questionnaire afterwards if s/he wishes, or to submit his/her questionnaire for a complete freeze of 
questionnaire data without the possibility of later modification. 
During the recording of the questionnaires, the logistics center will be able to contact the physician again 
if data are incomplete or inconsistent (checking of inconsistencies, non-responses and omissions) in order 
that corrections can be made by the participating physician before submission of the questionnaires. 
When the questionnaires are frozen, the data management company and the logistics center will receive 
the submitted and frozen questionnaires, which will then be directly integrated into the database as well 
as the "Pfizer study management" monitoring database. 
8.6.2. Compiling of the database 
An annotated questionnaire will be prepared by the CRO in charge of data management. This document 
will contain the name of the tables and the name of the variables. Each variable will be associated with its 
type, length and possible format. The annotated questionnaire will be sent to Pfizer for validation. 
The CRO will then construct a database using their own software. The structure of the database will be 
documented and verified on listings by comparing the attributes of database variables with the 
specifications noted on the annotated questionnaire. 
Before entering real data, the structure of the database and the entry screens will be tested and validated 
in accordance with the CRO's and Pfizer's standard operating procedures. To do so, fictitious 
questionnaires, generally 3 to 5, will be completed and captured. The validation will be done from scratch 
on lists of those data, then by comparison with the data recorded in the questionnaires. A validation 
report will be written and sent to Pfizer. The final structure of the database should be submitted for 
validation by Pfizer before entry of the actual data. 
An audit sheet will be produced in order to record all changes made to the database. The original datum, 
the modified datum, the date and time of the change, the person who made the change and the reason for 
the change will be recorded on the audit sheet. The functioning of the audit sheet will be tested by 
making changes to the fictitious data. A report will be written and sent to Pfizer. 
8.6.3. Data entry 
After validation of the database by Pfizer, the participating physician will be able to commence entering 
the data collected during the patients' visits into the study website. 
Periodic progress reports will be written by the CRO and sent to Pfizer for addition to the database. 
8.6.4. Data checking 
A list of consistency checks enabling the detection of inconsistencies and outlier responses present in the 
questionnaires will be compiled by the CRO and validated by Pfizer. These checks will be programmed 
using the CRO's own software, then tested using fictitious data. These fictitious data and the 
documentation relating to the tests will be kept in the study folder by the CRO and will be available for 
review by Pfizer. 
After data entry, the checks will be executed continuously. A specific query for each inconsistency will 
be generated electronically by the data checking system. 
The management of inconsistencies will be done in accordance with Pfizer's procedures. 
In order to limit the number of queries to be submitted to the participating physicians, an obvious 
corrections guide, prepared by the CRO and validated by Pfizer, could be prepared. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 27 of 89 
Following a simple request from Pfizer, the CRO shall make available the documentation regarding data 
checks. 
Periodic data check progress reports will be written by the CRO and sent to Pfizer. 
8.6.5. Coding 
This will be done using recognition software, a code and a preferred term, which will be allocated 
verbatim for coding. The dictionary chosen will be defined by Pfizer. 
8.6.6. Final quality control 
A final quality control will be conducted on a sample of √n + 1 patients selected at random. This 
quality control will be conducted in accordance with Pfizer's "CRF to database - QC guideline" guide. 
The acceptable error rate is 0.5%. 
A new sample will be selected if the rate calculated exceeds this threshold value. The CRO will write a 
summary of this quality control and will send it to Pfizer for review. 
8.6.7.  Database freeze 
The database freeze will not occur until the CRO has completed the entry and checking of data and final 
coding. The database freeze will be conducted in accordance with Pfizer's CT24 procedure. After 
validation by Pfizer, the database will be frozen by the CRO and prepared for statistical analysis. 
8.6.8.  Data management report 
A data management report will be written by the CRO after the database freeze and sent to Pfizer.  
8.6.9. Data transfer 
There will be no partial intermediate transfer of the database. At the end of the project, all of the paper 
and electronic documentation (database, programs and documents) will be transferred to Pfizer via CD-
ROM. 
 
8.7. Case report forms (CRFs)/Data collection tools (DCTs)/Electronic data record 
As used in this protocol, the term DCT should be understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method used in this study. 
A DCT is required and should be completed for each included patient.  The completed original DCT 
are the sole property of Pfizer and should not be made available in any form to third parties, except 
for authorized representatives of Pfizer or appropriate regulatory authorities, without written 
permission from Pfizer.  The investigator shall ensure that the DCTs are securely stored at the study 
site in encrypted electronic form and will be password protected or secured in a locked room to 
prevent access by unauthorized third parties. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, safety, and 
laboratory data entered on the DCTs and any other data collection forms (source documents) and 
ensuring that they are accurate, authentic/original, attributable, complete, consistent, legible, timely 
(contemporaneous), enduring, and available when required.  The DCTs must be signed by the 
investigator or by an authorized staff member to attest that the data contained on the DCTs are true.  
Any corrections to entries made in the DCTs or source documents must be dated, initialed, and 
explained (if necessary) and should not obscure the original entry. 
In most cases the source documents are the hospital or the physician's chart.  In these cases, data 
collected on the DCTs must match those charts.  

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 28 of 89 
In some cases, the DCT may also serve as the source document.  In these cases, a document should 
be available at the investigator site and at Pfizer that clearly identifies those data that will be 
recorded on the DCT, and for which the DCT will stand as the source document.  
8.7.1. Record retention 
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the To enable 
evaluations and/or inspections/audits from regulatory authorities or Pfizer, the investigator agrees to 
keep records, including the identity of all participating patients (sufficient information to link 
records, e.g., DCTs and hospital records), all original signed informed consent documents, copies of 
all DCT, safety reporting forms, source documents, detailed records of treatment disposition, and 
adequate documentation of relevant correspondence (e.g., letters, meeting minutes, and telephone 
call reports).  The records should be retained by the investigator according to local regulations or as 
specified in the clinical study agreement (CSA), whichever is longer.  The investigator must ensure 
that the records continue to be stored securely for so long as they are retained. 
If the investigator becomes unable for any reason to continue to retain study records for the required 
period (e.g., retirement, relocation), Pfizer should be prospectively notified.  The study records must 
be transferred to a designee acceptable to Pfizer, such as another investigator, another institution, or 
to an independent third party arranged by Pfizer.  
Investigator records must be kept for a minimum of 15 years after completion or discontinuation of 
the study or for longer if required by applicable local regulations.  
The investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met. 
 
8.8. Data analysis  
A detailed statistical analysis plan (SAP) will be written and will constitute the frame of reference with 
regards to statistical analyses. This analysis plan will be validated by the scientific committee and the 
study sponsor and will focus primarily on defining the populations studied as well as the statistical 
methods used. Any modification of the statistical methods described in the SAP should be reported and 
documented in the clinical/statistical report. 
Interim analysis 
An interim analysis, based on the descriptive analysis of the patients included and on the data collected, 
will be performed during the study. This analysis will be performed as soon as 20 patients presenting a 
complete response (cases) have been included and followed for 6 months. 
Statistics 
For the case and control groups, the quantitative data will be described by their population sizes, means, 
standard deviations, confidence intervals, medians and outlying values. The qualitative data will be 
described by their frequencies and percentages (95% bilateral confidence intervals will be provided 
where relevant). The number of missing data will also be recorded. 
All of the characteristics of the variables collected from cases and controls will be compared by the 
Student's t test for Gaussian quantitative data, the Mann-Whitney test for non-Gaussian quantitative data 
and the chi-squared test for qualitative data. The threshold of bilateral significance is set at 5%. 
Data will be analyzed using SAS software (version 9.1 - SAS Institute, North Carolina, USA). 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 29 of 89 
9. PROTECTION OF HUMAN SUBJECTS 
9.1. Patient information  
All parties will comply with all applicable laws, including laws regarding the implementation of 
organizational and technical measures to ensure protection of patient personal data.  Such measures 
will include omitting patient names or other directly identifiable data in any reports, publications, or 
other disclosures, except where required by applicable laws.  
 
The personal data will be stored at the study site in encrypted electronic and/or paper form and will 
be password protected or secured in a locked room to ensure that only authorized study staff have 
access. The study site will implement appropriate technical and organizational measures to ensure 
that the personal data can be recovered in the event of disaster.  In the event of a potential personal 
data breach, the study site shall be responsible for determining whether a personal data breach has in 
fact occurred and, if so, providing breach notifications as required by law. 
To protect the rights and freedoms of natural persons with regard to the processing of personal data, 
when study data are compiled for transfer to Pfizer and other authorized parties, patient names will 
be removed and will be replaced by a single, specific, numerical code, based on a numbering system 
defined by Pfizer.  All other identifiable data transferred to Pfizer or other authorized parties will be 
identified by this single, patient-specific code.  The investigator site will maintain a confidential list 
of patients who participated in the study, linking each patient’s numerical code to his or her actual 
identity.  In case of data transfer, Pfizer will maintain high standards of confidentiality and protection 
of patients’ personal data consistent with the clinical study agreement and applicable privacy laws. 
9.2. Patient consent 
The informed consent documents and any patient recruitment materials must be in compliance with 
local regulatory requirements and legal requirements, including applicable privacy laws. 
The informed consent documents used during the informed consent process and any patient 
recruitment materials must be reviewed and approved by Pfizer, approved by the institutional review 
board (IRB)/independent ethics committee (IEC) before use, and available for inspection. 
The investigator must ensure that each study patient or his or her legally acceptable representative, or 
parent(s) or legal guardian if a minor, is fully informed about the nature and objectives of the study, 
the sharing of data relating to the study and possible risks associated with participation, including the 
risks associated with the processing of the patient’s personal data.  The investigator further must 
ensure that each study patient, or his or her legally acceptable representative, or parent(s) or legal 
guardian if a minor, is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data. 
Whenever consent is obtained from a patient’s legally acceptable representative/parent(s) or legal 
guardian, the patient’s assent (affirmative agreement) must subsequently be obtained when the 
patient has the capacity to provide assent, as determined by the IRB/IEC.  If the investigator 
determines that a patient’s decisional capacity is so limited that he or she cannot reasonably be 
consulted, then, as permitted by the IRB/IEC and consistent with local regulatory and legal 
requirements, the patient’s assent may be waived with source documentation of the reason assent 
was not obtained.  If the study patient does not provide his or her own consent, the source documents 
must record why the patient did not provide consent (e.g., minor, decisionally impaired adult), how 
the investigator determined that the person signing the consent was the patient’s legally acceptable 
representative, the consent signer’s relationship to the study patient (e.g., parent, spouse), and that 
the patient’s assent was obtained or waived.  If assent is obtained verbally, it must be documented in 
the source documents. 

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9.3. Patient withdrawal 
Patients may withdraw from the study at any time at their own request, or they may be withdrawn at 
any time at the discretion of the investigator or sponsor for safety, behavioral, or administrative 
reasons.  In any circumstance, every effort should be made to document patient outcome, if 
applicable.  The investigator would inquire about the reason for withdrawal and follow-up with the 
patient regarding any unresolved adverse events.   
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be collected.  
The sponsor may retain and continue to use any data collected before such withdrawal of consent. 
9.4. Institutional review board (IRB)/Independent ethics committee (IEC) 
9.4.1. French Board of Physicians (CNOM) 
Pursuant to article L4113-6 (formerly L365-1) of the French Public Health Code, the following 
documents were sent by the sponsor of the study to the CNOM: 
• 
Final study protocol and amended version of 25/11/2013 
• 
Data collection questionnaire 
• 
List of physicians participating in the study and members of the scientific committee 
• 
Financial agreement proposed to participating physicians and to members of the scientific committee 
• 
Patient information leaflet and consent forms 
 
The study sponsor must inform the CNOM by registered letter of all financial matters between the 
sponsor, the members of the scientific committee and the physicians participating in the study. 
No response from the CNOM 2 months after receipt of the dossier indicates a favorable opinion. A copy 
of the proof of receipt will be sent by the sponsor to each participating physician. It is then the 
responsibility of each participating physician to send a copy of this proof of receipt and the financial 
agreement signed to the regional medical association to which s/he belongs. 
In the context of this case-control observational study, CENGEPS - Centre National de Gestion des 
Essais de Produits de Santé (French National Center for the Management of Health Products Trials) 
contracts are not applicable and can only be used for settling hospital overheads paid directly to the 
institution to which the participating physician belongs. 
9.4.2. Data protection French Data Protection Agency "CNIL" 
In accordance with French law no. 78-17 of January 6, 1978 on data protection, as amended by French 
law no. 2004-801 of August 6, 2004 on the protection of individuals with regard to treatment of personal 
data, this protocol has been subject to a request for an opinion from the CCTIRS - Comité Consultatif sur 
le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (French Advisory 
Committee for Data Processing in Health Research), which issued a favorable opinion on 18/01/2012. 
Following receipt of the favorable opinion from this committee, the computer file used to conduct the 
present study will be subject to a request for authorization from the French Data Protection Agency 
(CNIL). This computer file will be implemented following receipt of the authorization from CNIL; i.e. 
after 12/06/2012. 
9.4.3. Ethics Committee (EC) and declaration of the blood sample bank 
In this research, all of the procedures practiced and products used to treat those patients with metastatic 
renal cell carcinoma (mRCC) are those to which oncologists normally have recourse to. 
The conditions of use of Sunitinib and of other medication likely to be prescribed by the participating 
physicians during follow-up of the patients are compliant with their official indications and with their 
current methods of use, in accordance with the SmPC. 
In addition to the normal treatment of this kind of patient, and in order to better characterize those 
presenting CR with Sunitinib (followed or not followed by a recurrence), the protocol provides for 

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specific follow-up methods that involve only negligible risks and constraints for the patient. These 
specific methods consist of a 10 ml blood sample during inclusion on the trial (to identify biomarkers of 
CR) and a second sample taken in the event of a recurrence (to identify biomarkers predictive of the 
recurrence) for the cases group; a 10 ml blood sample during inclusion on the trial (to identify biomarkers 
predictive of the response), a 10 ml blood sample during follow-up at 6 months (to identify biomarkers 
predictive of the response), a 10 ml blood sample during follow-up at 12 months (to identify biomarkers 
predictive of the response) and, finally, a 10 ml blood sample during disease progression (to identify 
biomarkers predictive of the recurrence) for the control group. 
This bank of blood samples, collected for scientific research purposes, will help improve the therapeutic 
treatment of patients with metastatic renal cell carcinoma. 
Pursuant to articles L 1121-1-2° and R 1121-3 of the French Public Health Code, the protocol for this 
observational research was submitted to the Ile de France VII EC for the session on 07/12/2011. On 
February 13, 2012, the EC concluded that it was not empowered to issue an official opinion, the study not 
falling within the law governing biomedical research. It is of the opinion, however, that: 
- 
The rationale for this study is valid 
- 
The study is conducted under the ethical rules in force in France 
- 
The patient information leaflet is of good quality 
The informing of the patient will be the subject of a written document submitted to the EC. Express 
consent should be obtained from the patient before the start of the research. 
Moreover, as the blood is being collected to directly compile a collection of human biological samples, 
the provisions referred to in articles L 1243-3 and L 1243-4 apply, as well as the principles of 
compensation for injury and of insurance obligations as defined for biomedical research. 
The collection of samples was the subject of a prior declaration by the ANSM, formerly the AFSSAPS, 
dated 25/11/2013. 
9.4.4. Informing persons and obtaining their consent 
Persons participating in research must be informed about the purpose of the study, its duration, the 
number of participants, the purpose and methods of collecting blood samples to establish the sample 
bank, the method of reporting adverse events as well as their right to withdraw from the study. They must 
also be informed about the nature of the data sent, the intended use of the data, the recipients of those 
data and their right of access and of rectification as well as their right of opposition, in accordance with 
French law no. 78-17 of January 6, 1978 on data protection, as amended by French law no. 2004-801 of 
August 6, 2004 on the protection of individuals with regard to treatment of personal data. This 
information will be provided to the patients in writing via the document entitled "Patient information 
leaflet" appended to the study protocol and an informed consent form will have to be signed by the 
patient. 
The participating physician will countersign this consent form and will retain the original copy and 
provide the patient with a copy. 
Similarly, if an amendment to the protocol were to result in a revision of the patient information leaflets 
and informed consent forms, it would be the participating physician's responsibility to have these new 
forms signed by each patient participating in the research. This does not apply to patients who have 
completed the study. 
This personal information should be kept in the participating physicians file and be treated strictly 
confidential, but should be examinable by the competent authorities and duly authorized persons. 
9.4.5.  Ministry of research 
The participating physicians must collect blood samples from their patients. According to current French 
regulations, the Ministry of Research must be approached for a request for authorization to compile a 
collection of human biological samples. 

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Before the end of the research, the storage of the collection of biological samples will be declared to the 
Ministry of Research and to the director of the regional health authority (and submitted to the EC for 
opinion in the event of a change to the purpose of the research). 
9.4.6.  ANSM - Agence National de Sécurité du Médicament (The French National Agency for 
Medicines and Health Products Safety) 
In the case of a collection of human biological samples, the ANSM - Agence National de Sécurité du 
Médicament (The French National Agency for Medicines and Health Products Safety) wishes to be 
informed about the nature of the samples, the storage location as well as the purpose for compiling the 
collection. In order to do so, form FCEB280806 was sent to the ANSM on 25/11/2013. 
 
 
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS  
The reference document to use during this observational study is the SmPC for the Sutent® range, 
version no.: 001-01/14. 
REQUIREMENTS 
The table below summarizes the requirements for recording safety events on the electronic data capture  
and for reporting safety events on the non-interventional study (NIS) adverse event monitoring (AEM) 
Report Form to Pfizer Safety.  These requirements are delineated for three types of events: (1) serious 
adverse events (SAEs); (2) non-serious AEs (as applicable); and (3) scenarios involving drug exposure, 
including exposure during pregnancy, exposure during breast feeding, medication error, overdose, 
misuse, extravasation, and occupational exposure.  These events are defined in the section “Definitions 
of safety events”. 
Safety event 
Recorded on the electronic 
data capture  
Reported on the NIS AEM 
Report Form to Pfizer 
Safety within 24 hours of 
awareness 
SAE 
All 
All 
Non-serious AE 
All 
10.1. Poential reiks (PGR 
SUTENT V16.0) 
Carcinogénicity 
Potential Other cardiac events: 
Trouble of the conduction, 
Ischemic events 
Tachycardia 
Retinal abruption  
 
Missing important informations 
(PGR SUTENT V16.0) 
 
Pédiatric population 
Pregnancy and lactation 
Severe hepatic insufficiency 
Cardiac insufficiency 
 

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Safety event 
Recorded on the electronic 
data capture  
Reported on the NIS AEM 
Report Form to Pfizer 
Safety within 24 hours of 
awareness 
Scenarios involving exposure 
to a drug under study, 
including exposure during 
pregnancy, exposure during 
breast feeding, medication 
error, overdose, misuse, 
extravasation; lack of efficacy; 
and occupational exposure 
All (regardless of whether 
associated with an AE), 
except occupational 
exposure  
All (regardless of whether 
associated with an AE) 
 
For each AE, the investigator must pursue and obtain information adequate both to determine the 
outcome of the adverse event and to assess whether it meets the criteria for classification as a SAE 
(see section "Serious Adverse Events” below)  
Safety events listed in the table above must be reported to Pfizer within 24 hours of awareness of the 
event by the investigator regardless of whether the event is determined by the investigator to be 
related to a drug under study.  
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made immediately, 
irrespective of the extent of available event information. This timeframe also applies to additional 
new (follow-up) information on previously forwarded safety event reports. In the rare situation that 
the investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time of 
his/her first awareness of the events. 
For safety events that are considered serious or that are identified in the far right column of the table 
above that are reportable to Pfizer within 24 hours of awareness, the investigator is obligated to 
pursue and to provide any additional information to Pfizer in accordance with this 24-hour 
timeframe. In addition, an investigator may be requested by Pfizer to obtain specific follow-up 
information in an expedited fashion.  This information is more detailed than that recorded on the 
electronic data capture. In general, this will include a description of the adverse event in sufficient 
detail to allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications and 
illnesses must be provided.  In the case of a patient death, a summary of available autopsy findings 
must be submitted as soon as possible to Pfizer or its designated representative.  
 
Reporting period  
For each patient, the safety event reporting period begins at the time of  the patient’s first dose of 
Sutent or the time of the patient’s informed consent signed date if s/he is already exposed to Sutent, 
and lasts through the end of the observation period of the study, which must include at least 28 
calendar days following the last administration of a drug under study; a report must be submitted to 
Pfizer Safety (or its designated representative) for any of the types of safety events listed in the table 
above occurring during this period. 
If a patient was administered a drug under study on the last day of the observation period, then the 
reporting period should be extended for 28 calendar days following the end of observation. 
Most often, the date of informed consent is the same as the date of enrollment. In some situations, 
there may be a lag between the dates of informed consent and enrollment.  In these instances, if a 
patient provides informed consent but is never enrolled in the study (e.g., patient changes his/her 
mind about participation, the reporting period ends on the date of the decision to not enroll the 
patient.   

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If the investigator becomes aware of a SAE occurring at any time after completion of the study and 
s/he considers the SAE to be related to <the named drugs under study>, the SAE also must be 
reported to Pfizer Safety.  
 
Causality assessment 
The investigator is required to assess and record the causal relationship.  For all AEs, sufficient 
information should be obtained by the investigator to determine the causality of each adverse event.  
For AEs with a causal relationship to Sutent, follow-up by the investigator is required until the event 
and/or its sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer concurs 
with that assessment.   
An investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that Sutent caused or contributed to an adverse event. If the investigator’s final 
determination of causality is “unknown” and s/he cannot determine whether Sutent caused the event, 
the safety event must be reported within 24 hours.   
If the investigator cannot determine the etiology of the event but s/he determines that Sutent did not 
cause the event, this should be clearly documented on the electronic data capture and the NIS AEM 
Report Form.  
DEFINITIONS OF SAFETY EVENTS 
Adverse events 
An AE is any untoward medical occurrence in a patient administered a medicinal product.  The event 
need not necessarily have a causal relationship with the product treatment or usage. Examples of 
adverse events include but are not limited to:   
• Abnormal test findings (see below for circumstances in which an abnormal test finding 
constitutes an adverse event); 
• Clinically significant symptoms and signs; 
• Changes in physical examination findings; 
• Hypersensitivity; 
• Progression/worsening of underlying disease; <(Omit for Oncology and HIV studies)> 
• Lack of efficacy;  
• Drug abuse;  
• Drug dependency. 
Additionally, for medicinal products, they may include the signs or symptoms resulting from: 
• Drug overdose; 
• Drug withdrawal; 
• Drug misuse;  
• Off-label use;  
• Drug interactions; 
• Extravasation; 
• Exposure during pregnancy; 
• Exposure during breast feeding; 
• Medication error; 
• Occupational exposure. 
Abnormal test findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
adverse event are as follows:  

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• Test result is associated with accompanying symptoms, and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
• Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or 
• Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute 
an adverse event.  Any abnormal test result that is determined to be an error does not require 
reporting as an adverse event. 
Serious adverse events 
A serious adverse event is any untoward medical occurrence in a patient administered a medicinal or 
nutritional product (including pediatric formulas) at any dose Sutent:  
• Results in death; 
• Is life-threatening; 
• Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events); 
• Results in persistent or significant disability/incapacity (substantial disruption of the ability to 
conduct normal life functions); 
• Results in congenital anomaly/birth defect. 
 
Progression of the malignancy under study (including signs and symptoms of progression) should 
not be reported as a serious adverse event unless the outcome is fatal within the safety reporting 
period.  Hospitalization due to signs and symptoms of disease progression should not be reported as 
a serious adverse event.  If the malignancy has a fatal outcome during the study or within the safety 
reporting period, then the event leading to death must be recorded as an adverse event and as a 
serious adverse event with severity Grade 5.” 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or result in 
death or hospitalization.  However, if it is determined that the event may jeopardize the patient or 
may require intervention to prevent one of the other outcomes listed in the definition above, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or development 
of drug dependency or drug abuse. 
Additionally, any suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical symptoms or 
laboratory findings indicating an infection in a patient exposed to a Pfizer product.  The terms 
“suspected transmission” and “transmission” are considered synonymous.  These cases are 
considered unexpected and handled as serious expedited cases by PV personnel.  Such cases are also 
considered for reporting as product defects, if appropriate. 
 
Hospitalization 
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also includes 
transfer within the hospital to an acute/intensive care unit (e.g., from the psychiatric wing to a 
medical floor, medical floor to a coronary care unit, neurological floor to a tuberculosis unit). An 

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emergency room visit does not necessarily constitute a hospitalization; however, an event leading to 
an emergency room visit should be assessed for medical importance.  
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. For 
example, the following reports of hospitalization without a medical AE are not to be reported.  
• Social admission (e.g., patient has no place to sleep) 
• Administrative admission (e.g., for yearly exam) 
• Optional admission not associated with a precipitating medical AE (e.g., for elective cosmetic 
surgery) 
• Hospitalization for observation without a medical AE 
• Admission for treatment of a pre-existing condition not associated with the development of a new 
AE or with a worsening of the pre-existing condition (e.g., for work-up of persistent pre-
treatment lab abnormality) 
• Protocol-specified admission during clinical study (e.g., for a procedure required by the study 
protocol) 
 
Scenarios necessitating reporting to Pfizer Safety within 24 hours  
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication error, 
overdose, misuse, extravasation, lack of efficacy, and occupational exposure are described below. 
Exposure during pregnancy 
An exposure during pregnancy (EDP) occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been  exposed 
to (e.g., environmental) Sutent or the female becomes, or is found to be, pregnant after 
discontinuing and/or being exposed to Sutent (maternal exposure). 
An example of environmental exposure would be a case involving direct contact with a Pfizer 
product in a pregnant woman (e.g., a nurse reports that she is pregnant and has been exposed 
to chemotherapeutic products). 
2. A male has been exposed, either due to treatment or environmental exposure Sutent prior to 
or around the time of conception and/or is exposed during the partner pregnancy (paternal 
exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any source 
are reportable irrespective of the presence of an associated AE and  the procedures for SAE reporting 
should be followed. 
If a study participant or study participant’s partner becomes, or is found to be, pregnant during the 
study participant’s treatment with Sutent, this information must be submitted to Pfizer, irrespective 
of whether an adverse event has occurred using the NIS AEM Report Form and the EDP 
Supplemental Form.  
In addition, the information regarding environmental exposure to Sutent in a pregnant woman (e.g., a 
subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) must be submitted using the NIS AEM Report Form and the EDP supplemental form. This 
must be done irrespective of whether an AE has occurred.   
Information submitted should include the anticipated date of delivery (see below for information 
related to termination of pregnancy). 

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Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-up is 
conducted to obtain information on EDP outcome for all EDP reports with pregnancy outcome 
unknown.  A pregnancy is followed until completion or until pregnancy termination (e.g., induced 
abortion) and Pfizer is notified of the outcome.  This information is provided as a follow up to the 
initial EDP report.  In the case of a live birth, the structural integrity of the neonate can be assessed at 
the time of birth.  In the event of a termination, the reason(s) for termination should be specified and, 
if clinically possible, the structural integrity of the terminated fetus should be assessed by gross 
visual inspection (unless pre-procedure test findings are conclusive for a congenital anomaly and the 
findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, spontaneous 
abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live born, a 
terminated fetus, an intrauterine fetal demise, or a neonatal death]), the procedures for reporting 
SAEs should be followed. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
• Spontaneous abortion includes miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs when 
the investigator assesses the infant death as related or possibly related to exposure to 
investigational product 
Additional information regarding the exposure during pregnancy may be requested.  Further follow-
up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on preterm infants to 
identify developmental delays).   
In the case of paternal exposure, the study participant will be provided with the Pregnant Partner 
Release of Information Form to deliver to his partner.  It must be documented that the study 
participant was given this letter to provide to his partner. 
Exposure during breastfeeding 
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of an 
associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (e.g., vitamins) is administered in accord with 
authorized use. However, if the infant experiences an AE associated with such a drug’s 
administration, the AE is reported together with the exposure during breastfeeding. 
Medication error 
A medication error is any unintentional error in the prescribing, dispensing or administration of a 
medicinal product  that may cause or lead to inappropriate medication use or patient harm while in 
the control of the health care professional, patient, or consumer.  Such events may be related to 
professional practice, health care products, procedures, and systems including: prescribing; order 
communication; product labeling, packaging, and nomenclature; compounding; dispensing; 
distribution; administration; education; monitoring; and use.   
Medication errors include: 
• Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or prescription on 
the part of the healthcare provider or the patient/consumer); 
• Confusion with regard to invented name (e.g., trade name, brand name). 

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The investigator must submit the following medication errors to Pfizer, irrespective of the presence 
of an associated AE/SAE : 
• Medication errors involving patient exposure to the product, whether or not the medication 
error is accompanied by an AE. 
• Medication errors that do not involve a patient directly (e.g., potential medication errors or 
near misses).  When a medication error does not involve patient exposure to the product the 
following minimum criteria constitute a medication error report: 
• An identifiable reporter; 
• A suspect product; 
• The event medication error. 
 
Overdose, Misuse, Extravasation 
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.  
Lack of Efficacy 
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, irrespective 
of the presence of an associated AE/SAE or the indication for use of the Pfizer product. 
Occupational Exposure 
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE. 
Communication problems  
In case of prohibition or restriction (eg clinical hold) by a competent authority in any region of the 
world, or if the investigator is aware of any new information that may influence the evaluation of the 
benefits and risks of Sutent, Pfizer must be informed immediately.  
In addition, Pfizer will inform the investigator immediately of any urgent safety measure taken by 
the investigator to protect patients in the trial against any immediate danger, and any serious 
violation of the Memorandum of NI study in which the investigator is aware. 
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
Any information obtained from this research will be treated as confidential until the analysis and final 
review by Pfizer and by members of the scientific committee has been carried out. 
The results of the study may be published or presented by members of the scientific committee after 
review and approval by Pfizer, such that confidential or proprietary information is not disclosed. Before 
publication or presentation, a copy of the final text should be sent by the member(s) of the scientific 
committee to Pfizer for comment. Such comments will aim to ensure the scientific content of proposed 
publications and/or presentations and to ensure that data and materials relating to Pfizer's products and 
activities are presented fairly, accurately and reasonably. 
 
12. REFERENCES 
1. 
Projections de l’incidence et de la mortalité par cancer en France en 2009. Données 
disponibles sur le site de l’INVs. 
http://www.invs.sante.fr/applications/cancers/projections2009/rapport_projections_national
es_cance r_2009.pdf 

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2. 
Survie attendue des patients atteints de cancers en France : état des lieux – avril 2010. 
Disponible sur le site de l’INCa : http://www.e-cancer.fr/les-soins/4211-survie-des-
patientsatteints-de-cancers-en-france-linca-dresse-un-etat-des-lieux 
3. 
HAS – Institut National du Cancer. Guide ALD. Tumeur maligne, affection maligne du 
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6. 
Motzer RJ, Bukowski RM, Figlin RA et al. Prognostic nomogram for in patients with 
metastatic renal cell carcinoma. Cancer 2008; 113 (7): 1552-8. 
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Motzer RJ, Hutson TE, Tomczak P et al. Overall survival and updated results for compared 
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8. 
Heng DY, Rini B, Garcia J et al. Prolonged complete responses and near-complete 
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Albiges L, Oudard S, Negrier S et al. Complete remission with TKI in renal cell carcinoma: 
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12. Neill MG, Wei AC, Jewett MAS et al. Consolidative renal cell carcinoma metastasectomy 
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13. Rini B, Atkins M. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 
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14. Zama IN, Hutson TE, Elson P et al. Sunitinib Rechallenge in Metastatic Renal Cell 
Carcinoma Patients Cancer 2010; 116: 5400–6. 
15. Johannsen M, Staehler M, Ohlmann CH et al. Outcome of treatment discontinuation in 
patients with metastatic renal cell carcinoma and no evidence of disease following targeted 
therapy with or without metastasectomy. Ann Oncol 2011; 22: 657-63. 
16. Jain RK, Duda DG, Willett CG et al. Biomarkers of response and resistance to 
antiangiogenic therapy. Nature Rev Clin Oncol 2009; 6(6): 327-38. 
17. Huang D, Ding Y, Zhou M et al. Interleukin-8 mediates resistance to antiangiogenic agent 
in renal cell carcinoma Cancer Res 2010; 70:1063-71. 
18. Eisenhauer EA, Therasseb P, Bogaerts J. New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1) Eur J Cancer 2009; 45: 228-47. 
19. HAS, Guide affection longue durée, Tumeur maligne, affection maligne du tissu 
lymphatique ou hématopoïétique, Cancer du rein de l’adulte, Juin 2010. 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 40 of 89 
 
13. APPENDIX 
13.1. APENDIX 1. Sae form 
 
Etude non-interventionnelle : 
Formulaire de notification 
d’évènements indésirables  
Cadre réservé à Pfizer 
Numéro AER 
      
Date de notification à 
Pfizer 
      
Ecrire toutes les dates au format JJ/MMM/AAAA 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
  
  
  
NUMÉRO DE PROTOCOLE / ÉTUDE 
 
NUMÉRO DE CENTRE 
 
IDENTIFICATION PATIENT/NUMERO DE RANDOMISATION 
Titre du protocole :       
 Rapport initial 
 Rapport 
de suivi 
 
Pays de survenue de l’évènement :       
Données Patient 
Age       
 
Taille       cm 
Origine ethnique : 
 Homme 
 Femme 
Poids       kg 
  La réglementation locale interdit 
de poser la question 
Si le patient est 
décédé: 
Date de décès :       
Cause du décès :       
Autopsie réalisée 
 OUI 
 NON 
 
INCONNU 
Si oui, quelle est la cause du décès 
déterminée à l'autopsie :         
Antécédents du patient 
□
  Aucun  
□
  Inconnu 
Noter ci-dessous les antécédents médicaux pertinents. Inclure les autres pathologies présentes au moment de 
l'événement et les antécédents médicaux préexistants. Si la place prévue ici n'est pas suffisante, utiliser des 
exemplaires supplémentaires de la page. 
Maladie (préciser) 
Date de 
survenue 
Date de 
fin 
Cocher la case si 
maladie en cours 
Informations pertinentes incluant les 
interventions chirurgicales et leurs dates 
      
      
      
 
      
      
      
      
 
      
      
      
      
 
      
Médicament à l’étude, 
Forme pharmaceutique, 
Voie d’administration 
Cocher 
la case 
si 
produit 
Pfizer 
Dosage 
Unités 
Fréquence 
Date de 
début 
Date de fin 
Cocher la case 
si médicament 
en cours 
      
 
      
      
      
      
      
 
      
 
      
      
      
      
      
 
      
 
      
      
      
      
      
 
Médicaments 
concomitants 
 
 Aucun  
 
Inconnu 
Reporter ci-dessous les médicaments concomitants pris dans les 2 semaines précédant la survenue de l’évènement. Exclure tous 
les médicaments pris seulement plus de 2 semaines avant la survenue de l’évènement et tous les médicaments utilisés pour traiter 
l’évènement ou pris après l’apparition de l’évènement. Si vous manquez d’espace, veuillez utiliser plusieurs copies de cette 
page. 
Nom du médicament  
(marque déposée et DCI) 
Indication 
Voie 
d’administration 
Date de 
début 
Date de fin 
Cocher la case 
si médicament 
en cours 
      
      
      
      
      
 
      
      
      
      
      
 
      
      
      
      
      
 
Examens complémentaires 
pertinents 
Reporter seulement les résultats d’examens complémentaires pertinents par rapport à l’(aux) évènement(s), par exemple, analyse 
de laboratoire et résultat d’imagerie. Si vous manquez d’espace, veuillez utiliser plusieurs copies de cette page. 
Examen 
Date 
Résultat 
Unités 
Valeurs normales 
Commentaires 
Limite 
inférieure 
Limite 
supérieure 
      
      
      
      
      
      
      
      
      
      
      
      
      
      
 
Version 3, mai 2012 
Page ___ de ___ 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 41 of 89 
 
Etude non-interventionnelle : 
Formulaire de notification d’évènements 
indésirables  
Cadre réservé à Pfizer 
Numéro AER 
      
Ecrire toutes les dates au format JJ/MMM/AAAA 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
  
  
  
NUMÉRO DE PROTOCOLE / ÉTUDE 
 
NUMÉRO DE CENTRE 
 
IDENTIFICATION PATIENT/NUMERO DE 
RANDOMISATION 
EVENEMENTS INDESIRABLES GRAVES (si plus de 2, utiliser des copies supplémentaires de cette page) 
S’il est connu, indiquer le diagnostic plutôt que les signes et symptômes. 
Evènement indésirable:       
Evènement indésirable:       
Date de survenue :       
 
Date de survenue :       
 
L’évènement est-il grave ? : 
 OUI 
 NON 
L’évènement est-il grave ? : 
 OUI 
 NON 
Si oui, préciser ci-dessous les critères de gravité :  
Si oui, préciser ci-dessous les critères de gravité :  
Critère de gravité (un ou plusieurs choix possibles) : 
 A entraîné le décès 
 Menace du pronostic vital 
 Hospitalisation/Prolongation d’hospitalisation 
 Invalidité/incapacité permanente ou importante 
 Anomalie / malformation congénitale 
 Evènement médicalement important 
Critère de gravité (un ou plusieurs choix possibles) : 
 A entraîné le décès 
 Menace du pronostic vital 
 Hospitalisation/Prolongation d’hospitalisation 
 Invalidité/incapacité permanente ou importante 
 Anomalie / malformation congénitale 
 Evènement médicalement important 
Evolution au moment de ce rapport ou au moment du décès : 
Evolution au moment de ce rapport ou au moment du 
décès : 
 Guéri 
}         Date de guérison :               
 Guéri avec séquelles 
} 
 En cours de guérison 
 Non Guéri 
 Inconnu 
 Guéri 
}         Date de guérison :          
 Guéri avec séquelles 
} 
 En cours de guérison 
 Non Guéri 
 Inconnu 
Existe-t-il une possibilité raisonnable que l'événement soit lié au 
médicament à l'étude :      
 OUI 
 NON 
Existe-t-il une possibilité raisonnable que l'événement soit 
lié au médicament à l'étude :      
 OUI 
 NON 
 
Si oui, préciser le médicament à l'étude :                    
 
 
Si oui, préciser le médicament à l'étude :                    
 
Existe-t-il une possibilité raisonnable que l'événement soit lié à 
un médicament concomitant :      
 OUI 
 NON 
 
Si oui, préciser le médicament concomitant :              
Existe-t-il une possibilité raisonnable que l'événement soit 
lié à un médicament concomitant :      
 OUI 
 NON 
 
Si oui, préciser le médicament concomitant :            
Dernière action entreprise pendant le ou les événements, 
préciser le nom du médicament : 
Dernière action entreprise pendant le ou les événements, 
préciser le nom du médicament : 
                                            
                                            
 
                                           
 
                                           
 
 Arrêt (temporaire ou 
permanent, ou prise décalée) 
 Diminution de posologie 
 Augmentation de posologie 
 Posologie inchangée 
 Inconnu 
 Ne s’applique pas 
 Arrêt (temporaire ou 
permanent, ou prise décalée) 
 Diminution de posologie 
 Augmentation de 
posologie 
 Posologie inchangée 
 Inconnu 
 Ne s’applique pas 
 Arrêt (temporaire ou 
permanent, ou prise décalée) 
 Diminution de posologie 
 Augmentation de 
posologie 
 Posologie inchangée 
 Inconnu 
 Ne s’applique pas 
 Arrêt (temporaire ou 
permanent, ou prise décalée) 
 Diminution de posologie 
 Augmentation de 
posologie 
 Posologie inchangée 
 Inconnu 
 Ne s’applique pas 
Un EI/EIG est-il réapparu lors de la ré-administration du médicament ? 
 Oui   
 Non   
 Inconnu  
 Sans objet  
Si oui, quel(s) EIG/EI :       
Histoire de l’évènement (Narratif) : Merci de bien vouloir fournir toute information concernant cet évènement qui ne serait pas rapportée dans un autre champ 
de ce formulaire (circonstances, chronologie, diagnostic et traitement symptomatique). Si vous manquez d’espace, veuillez utiliser plusieurs copies de cette page. 
 
Personne du centre effectuant la 
notification pour le centre :  
      
 
 
      
 
 
Nom et prénom EN LETTRES CAPITALES 
 
 
Date 
 
Adresse : 
      
 
      
 
      
 
      
 
 
Rue 
 
Ville 
 
Code postal 
 
Pays 
 
N° de téléphone : 
      
N° de fax : 
      
E-mail : 
      
Nom de l’investigateur si différent : 
      
Date de prise de connaissance par 
l’investigateur (ou nidificateur) : 
_____-_____-_____ 
Signature de l’investigateur : 
 
 JJ 
MMM 
AAAA 
Version 3, mai 2012 
Page ___ de ___ 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 42 of 89 
 
13.2. Appendix 2: National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) 
NCI CTCAE (version 4.0) are the reference criteria for this protocol.  
The following link provides access to the NCI CTCAE criteria:  
http://ctep.cancer.gov/reporting/ctc.html 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 43 of 89 
 
13.3. Appendix 3: Information letter and consent form for patient with mRCC in CR with 
Sunitinib (Case) 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 38 of 89 
 
PART I 
I 
NATURE AND AIM OF THE STUDY 
This document is called a patient information letter and informed consent form. It contains detailed explanations about the 
observational study that you have been invited to participate in as well as a consent form, which you will be required to complete if you 
decide to participate. You have been invited to participate in this study conducted by Pfizer because you are currently receiving 
treatment for metastatic renal cell carcinoma. 
You are being or have been treated with SUTENT® for your renal carcinoma and, thanks to the treatment, your disease is currently in 
complete remission, as has been confirmed by radiological examinations. Our aims are to identify the characteristics of patients 
(clinical or biological) who develop complete remission of renal cell carcinoma and to also search for factors that may favor a possible 
recurrence of the disease. Long-term, such research aims to improve the therapeutic management of patients with metastatic renal 
cell carcinoma. 
It is a cross-sectional then longitudinal, comparative, multicenter, prospective, observational study with collection of blood samples. 
II 
PROJECT ORGANIZATION 
A 
STUDY PROCEDURES 
The protocol for this research provides for you to be followed for 3 years and to have one blood sample taken (or two samples if there 
is a recurrence during this 3-year period) in order to assay certain substances in it the presence of which might be associated with the 
development of complete remission or a recurrence (these substances are called "biological and genetic markers"). Apart from these 
blood samples, this research does not affect the treatment of your disease. 
Your participation in this study will involve: 
• Authorizing the physician to collect personal data about the characteristics of your cancer, the treatments received to date 
and your possible associated diseases. 
• Authorizing the physician to ask sending and collection of your histological sample before the initiation of Sunitinib  
• Having a blood sample collected of approximately 2 x 5 ml for analysis of biological and genetic markers in association 
with the complete remission of your cancer. Your blood sample will be labeled anonymously. 
• In the event of a recurrence of your renal cell carcinoma, completing a second questionnaire on the characteristics of the 
recurrence as well as having a second blood sample of 2 x 5 ml collected to identify the biological and genetic markers 
associated with this recurrence. 
• As with all sample collection, these blood samples may cause a slight pain or cause a bruise to appear on your arm at the 
collection site. 
During the research, all of the samples collected from subjects participating in the research will be sent and stored at the Institut 
Gustave Roussy laboratory (114 rue Edouard Vaillant, 94800 Villejuif, France) in order to perform the screening of biological and 
genetic markers. The storage of these samples will be the responsibility of the directors of those laboratories. 
The biological and genetic samples collected will be used exclusively for the research. 
By accepting to participate in this study, you’ll validate your participation and will be included in the study 
By accepting to participate in this study, you also consent to the future use of these samples for anything that concerns the objective 
of the study. Indeed, new markers will probably be identified as scientific knowledge advances. 
 
At any moment, if you changed your opinion, you can ask the destruction of your samples in asking it to your physician. The sample 
will be destructed 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016 
Patient's 
initials 
Patient information leaflet and informed 
consent form 
Page: 1 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 39 of 89 
 
 
B 
PLANNED DURATION OF THE STUDY AND PLANNED NUMBER OF PATIENTS 
If you decide to participate in this study, you will be one of 40 subjects with metastatic renal cell carcinoma treated with SUTENT®, 
and whose disease is in complete remission, included by one of the participating sites located in metropolitan areas throughout 
France. 
This study will not change your relationship with your physician, who may prescribe any procedure during this consultation, if he 
deems it to be necessary. 
C 
RESTRICTIONS ASSOCIATED WITH THE STUDY AND INFORMATION FOR THE PATIENT 
This study does not have any restrictions that you need to observe. 
Should the study result in any harm to you, in compliance with current French law, you will be covered during the entire study by 
insurance taken out by the sponsor Pfizer. 
Contact details of the person to contact for additional information or in case of injury related to the study: 
_________________________ 
_________________________ 
III 
RESPONSABILITIES, PATIENT'S RIGHTS AND CONFIDENTIALITY 
A 
WITHDRAWAL FROM STUDY 
The participating physician, i.e. the physician who suggests this study to you, or the sponsor may decide to discontinue your 
participation in this study, if: 
a) 
You do not follow the participating physician's instructions 
b) 
You develop a serious condition that would require discontinuation of treatment 
c) 
The study is stopped by the sponsor or the health authorities 
B 
RIGHTS 
Your participation in this study is voluntary and entirely of your own free will. Please take the time to read this information leaflet and 
discuss it with your physician and your family, if you wish. Do not hesitate to ask your physician any questions if you require further 
information. If you decide not to participate or withdraw from the study for any reason whatsoever, this shall not affect your relationship 
with the physician who is monitoring you as part of this study, or with your attending physician. If you change your mind and decide not 
to participate in this supplementary study, you can ask for the destruction of your samples by approaching the study physician. The 
samples will then be destroyed. 
If you have any questions during the course of the study, you should contact the physician monitoring you as part of this study. 
Pursuant to French law, the protocol describing the study in which you are participating received a favorable opinion from the CCTIRS 
- Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (French Advisory 
Committee for Data Processing in Health Research) on 18/01/2012. The committee is charged with verifying the scientific relevance of 
the trial, the conditions required for your protection and the upholding of your rights. 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016 
Patient's initials
 
Patient information leaflet and informed consent 
form 
Page:  
2 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 
11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone 
b
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 40 of 89 
 
 
 
The drawing of blood samples was the subject of a prior declaration by the competent authority [ANSM - Agence Nationale de 
Sécurité du Médicament (The French National Agency for Medicines and Health Products Safety)]. 
If you want, your attending physician will be informed about your participation in this study. 
Following analysis of the data for all patients, you will be informed of the overall results of this study via the physician monitoring you 
as part of this study. 
 
C 
DATA CONFIDENTIALITY 
All medical records and documentation from this study that identify you will be kept strictly confidential and will not be subject to any 
disclosure to third parties, to the extent permitted by French laws and/or regulations currently in force. The data gathered regarding 
you that are identified by a code number will remain anonymous for the future analysis of study results. If the overall results from this 
study are likely to be communicated or published in the medical literature, only anonymized data will be presented. 
In the context of the present study, you accept that designated representatives of the health authorities, representatives of Pfizer, 
other physicians, nurses and people participating in this study will have access to medical records about you. You agree that these 
documents shall be communicated under the conditions described above, even if you decide to withdraw from this study. 
Data about you recorded during this study for epidemiological evaluation, including data about your lifestyle, will be subject to 
computer processing by or on behalf of Pfizer. In accordance with French law no. 78-17 of January 6, 1978 on data protection, as 
amended by French law no. 2004-801 of August 6, 2004 on the protection of individuals with regard to treatment of personal data, you 
may exercise your rights of access to and rectification of your data. You can exercise those rights at any time by contacting the 
physician monitoring you as part of the study. 
Pfizer owns the data, will control their use and will take all necessary measures to ensure their protection. 
 
IV 
PARTICIPATING PHYSICIAN'S COMPENSATION 
The participating physician receives financial compensation from the sponsor for this study. 
 
 
 
 
 
 
 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016 
Patient's initials 
 
 
Patient information leaflet and informed consent 
form 
Page:  
3 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 
11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone 
b
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 41 of 89 
 
 
CONSENT FORM FOR PARTICIPATION IN THE STUDY 
Dr  .........................................  invited me to participate in a study conducted by Pfizer on the treatment of metastatic renal cell carcinoma 
entitled: "A PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL 
CELL CARCINOMA" 
I have reached the age of majority. 
I belong to a social security scheme or am a beneficiary of such a scheme. 
I have read the information above and have fully understood it. I was given the time and opportunity to ask any questions I wanted to about 
the study and this form. 
I have read all pages of this consent form and have understood the risks and benefits described. 
I have been informed that I will be covered by insurance taken out by the sponsor, Pfizer, pursuant to current French legislation. 
I understand that data concerning me will remain strictly confidential. I consent to them being consulted only by members of Pfizer, their 
representatives, any service providers under contract to Pfizer and by the various regulatory authorities, provided that Pfizer is committed to 
respecting the confidentiality of the data pursuant to law no. 78-17 of January 6, 1978. 
I accept that the data recorded during this study will be subject to computerization by Pfizer or on its behalf. I understand that my right of 
access and of rectification, as provided by law no. 78-16 of January 6, 1978 relating to data processing, data files and individual liberties, as 
amended by law no. 2004-801 of August 6, 2004 relating to the protection of individuals with regard to the processing of personal data, may 
be exercised at any time from Pfizer via the physician monitoring me during this study. 
It was explained to me that I am free to accept or refuse to participate in this study and to withdraw from the study at any time without this 
changing my relationship with my physician. Signature of this consent form does not discharge Pfizer from its responsibilities and I retain all 
my rights as guaranteed by law. 
I agree that the results of the study may be published and communicated to the authorities concerned and to Pfizer. I freely agree to 
participate in this study under the conditions specified in this document. 
By signing this consent form I confirm that all of the information I have provided, particularly concerning my medical history, is accurate to the 
best of my knowledge. 
I understand that I will be given a copy of this signed consent form. 
The patient 
Surname / First name in capital letters: 
___________________________________ 
Date: ---------------------------  
Patient's signature: 
The participating physician 
Surname / First name of participating physician in capital letters: 
Dr / Prof: -----------------------------------------------------------------------------------------------  
Date: ---------------------------------------------------------------------------   
Participating physician's signature: 
 
Sponsor: 
PFIZER 
 
23-25, avenue du Dr Lannelongue  
 
75668 PARIS Cedex 14, France 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016
 
Patient information leaflet and informed consent 
form 
Page:  
4 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 
11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone 
b
Name of patient 

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Part II 
 
Study title: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC 
RENAL CELL CARCINOMA 
 
Use and storage of blood samples for 
 research 
 
Investigator's name: 
Telephone number 
Name of patient: 
 
Part I of this consent form describes the main part of the biomedical research on SUTENT®. 
Part II below requires your consent in order to be able to use a blood and histological sample to study your genes, also called DNA and 
cellular biomarkers. 
However, if you do not want to provide these additional samples, you can still participate in the main study described in Part I of the consent 
form. 
WHAT IS THE PURPOSE OF THIS RESEARCH? 
Blood contains genes. The genes provide instructions that govern different processes taking place in the body and physical characteristics 
such as eye color. Genes differ slightly from one person to another. Information on these differences between individuals allows researchers 
to learn more about diseases, the best way to treat them and to understand how each one responds to medication. 
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The objective of this study is to collect, store and use your blood sample to study the genes, RNA, proteins and metabolites. Your sample will be 
studied only with reference to the following: 
x Analysis of genetic polymorphisms of VEGF-A (SNPs) in patients receiving Sunitinib in CR (cases) and selected as controls. 
x To determine whether this polymorphism correlates with complete remission or progression. 
x To determine whether polymorphisms of VEGF can reduce the response rate of patients receiving Sunitinib. All information 
enabling it to be identified as your sample will be deleted. 
 
 
 
 
 
 
This research could contribute to developing new treatments or improving existing treatments. The sample will be stored until it is used up or 
destroyed at Pfizer's discretion of, which may take several years. The information obtained following its analysis will be saved indefinitely. This 
will allow researchers to continue their investigations on genes in the future that have not yet been discovered today. 
No genetic research in addition to the objectives described above will be carried out. 
The samples will be stored by the Institut Gustave Roussy (IGR), 114 rue Edouard Vaillant, 94800 Villejuif, France.  
Pursuant to current French legislation: 
x The protocol describing this research: 
o
Has received a favorable opinion from CCTIRS - Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le 
domaine de la Santé (French Advisory Committee for Data Processing in Health Research). 
o
Has been declared to the competent authority [ANSM - Agence Nationale de Sécurité du Médicament (The French National Agency for 
Medicines and Health Products Safety)]. 
x Pfizer has taken out civil liability insurance covering any health problems in connection with your participation in this research. 
 
WHAT WILL HAPPEN IF I PARTICIPATE IN THIS RESEARCH? 
If you participate in this research, analyzes will be done on samples taken in the context of this observational study. ON : 
x
9*()$6136*HQHWLFSRO\PRUSKLVP
x
&HOOXODUPDUNHr 
 
WHAT ARE THE BENEFITS ASSOCIATED WITH MY PARTICIPATION? 
You are not expected to benefit from your participation in this supplementary research. On the other hand, the knowledge acquired thanks to this 
research may benefit other people. 
 
WILL MY DATA BE CONFIDENTIAL? 
As described in Part I, all data will remain strictly confidential and anonymized. The results of this part of the study are liable to be published for 
scientific purposes, but under no circumstances will your identity be revealed. Consequently, neither you nor any other person will be able to 
obtain the results of any genetic analysis performed on your sample. 
Before being relabeled, your sample will be treated as "sensitive personal data". 
By participating in this study, you agree that (1) the research team, (2) Pfizer's representatives and authorized companies, (3) the EC that 
approved this study and (4) national and international regulatory authorities can have access to and examine your medical records in order to (a) 
conduct the study, (b) check the accuracy of the data, (c) monitor that it is being conducted in accordance with good clinical practice and the law 
and (d) conduct other research associated with the study. 
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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 44 of 89 
 
 
 
WHO WILL HAVE OWNERSHIP OF MY SAMPLE(S)? 
Pfizer will ensure that the samples are used in accordance with the objectives of this supplementary study, the associated informed consent 
form and the ethical approval received. 
The study sponsor will not sell or transfer ownership of the sample to any third parties. The samples will only be used by Pfizer and/or 
researchers working with Pfizer, and only as part of the research study described above. Pfizer may use information from your sample in 
order to develop products or procedures from which it may make a profit. Pfizer intends to retain the exclusive rights to any products and 
processes that are developed using information from your sample. You will not receive any payments for products of any kind that are 
developed thanks to this research. 
 
WHAT WILL HAPPEN IF I DECIDE TO NO LONGER PARTICIPATE IN THE STUDY? 
If you change your mind and decide not to participate in this supplementary study, you can ask for the destruction of your samples by 
approaching the study physician (in this case, they will be destroyed). However, once your identity no longer appears on the sample (during 
the analyses), it will no longer be possible to have it destroyed. 
Your participation in this biomedical research is voluntary and entirely of your own free will. If you decide not to participate in it or you 
withdraw from this research for any reason whatsoever, you will continue to receive the same advantages that you were able to before. This 
will in no way affect your relationship with the physician monitoring you as part of this research, as well as with your attending physician. If 
you so wish, you may be given time to reflect. 
If you decide to withdraw from this research, you must inform the study physician. In the absence of this information from you, s/he will be 
required to contact you again in order to confirm your decision. If you withdraw from the study, no new information concerning you will be 
collected, however information that has already been collected may be used. 
 
MY CONTACT DETAILS 
Consenting to this supplementary part of the study is completely optional and separate from the consent given to participation in the clinical 
study on the medicinal product (Part I). 
Before deciding to participate in this part of the study, you will be given time to study the information contained in this form. If you have any 
questions regarding this research and/or your rights, please contact: 
 
NAME OF PHYSICIAN TO CONTACT 
Telephone number 
Dr / Prof: 
Tel.:  
Email: 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016
 
Patient information leaflet and informed consent 
form 
Page:  
7 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 
11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone 
b
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 45 of 89 
 
 
CONSENT FORM FOR PARTICIPATION IN THE STUDY 
Study title: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL 
CELL CARCINOMA 
Dr  Invited me to participate in an observational study organized by Pfizer. 
This consent form relates to the supplementary pharmacogenomics study to 
describe the characteristics of patients with mRCC and presenting CR (Cases) 
with Sunitinib and to compare them with the characteristics of patients with 
mRCC and not presenting CR (Controls) with Sunitinib in order to identify factors 
associated with the occurrence of complete remission. 
I have understood the information above. I was given the time and opportunity to 
ask any questions I wanted to about the research and this form and all of my 
questions were answered. 
It was explained to me that I am free to accept or refuse to participate in this 
study and to withdraw from the study at any time without this changing my 
relationship with my physician. Signature of this consent form does not discharge 
Pfizer from its responsibilities and I retain all my rights as guaranteed by law. 
By signing this consent form, I confirm that: 
• 
I have reached the age of majority 
 
• 
I belong to a social security scheme or am a beneficiary of such a 
scheme. 
I was informed that: 
• 
I will be covered during this biomedical research by the insurance 
taken out by Pfizer. 
• 
Data pertaining to me will remain strictly confidential. I authorize 
access to the data to Pfizer, its representatives, any service provider 
under contract to Pfizer and the various regulatory authorities. 
I accept that: 
• 
The data recorded during this research will be subject to 
computerization by Pfizer or on its behalf. I understand that I may 
exercise my right of access and rectification from Pfizer at any time via 
the physician monitoring me for this research. 
• 
The data will be collected, used and transferred in accordance with the 
conditions described. 
I therefore freely agree to participate in this biomedical research under the conditions specified in this document and a signed copy of this patient 
information leaflet and informed consent form will be returned to me. 
The patient (Surname / First name of patient in capital letters) 
The participating physician (Surname / First name of participating physician 
in capital letters) 
----------------------------------------------------------------------------- 
Dr / Prof ------------------------------------------------------------------------- 
Patient's signature: 
Date: ------------------------- 
Participating 
physician's 
signature: 
Date: ------------------------- 
The impartial witness * / legal guardian / family member ** / 
trusted person ** / guardianship judge 
* Impartial witness: a person who actually attended an event and can validly 
attest to this. S/he has no personal interest in the patient's consenting and is 
totally independent of the investigator and of the sponsor. 
** Trusted person / Family member: person, freely chosen by the patient from 
his/her circle of family and friends and in whom s/he has complete confidence 
independent of the context of the clinical trial and who cannot be unfairly 
influenced. This person assists with informing the patient and with the obtaining 
of the informed consent if the patient or his/her legal guardian are unable to 
read. S/he reads the informed consent form and all other written information 
given to the patient. 
* & ** pursuant to the articles of the French Public Health Code: article L 1122-
1-1 and article L 1111-6. 
__________________________________________ 
Surname / First name in capital letters 
_______________________  
_____________ 
Signature  
Date 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC in complete remission with Sunitinib (Case) 
Version dated April 11, 2016
 
Patient information leaflet and informed consent 
form 
Page:  
8 of 8 
PATIENT IN COMPLETE REMISSION - CASES 
 
Protocol no.: A6181209 
Date: 
11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone 
b
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 46 of 89 
 
 
13.4. Appendix 4: Patient information leaflet and consent form for patients with mRCC selected as 
controls and treated with Sunitinib 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 35 of 172 
 
PART I 
I 
NATURE AND AIM OF THE STUDY 
This document is called a patient information letter and informed consent form. It contains detailed explanations about the observational study that you have 
been invited to participate in as well as a consent form, which you will be required to complete if you decide to participate. You have been invited to participate in 
this study conducted by Pfizer because you are currently receiving treatment for metastatic renal cell carcinoma. 
You will be treated for metastatic renal cell carcinoma with a targeted therapy called SUTENT®. Our aims are to identify the characteristics of patients (clinical or 
biological) likely to favor complete remission (CR) of renal cell carcinoma with SUTENT® and to also search for factors that may favor a possible recurrence of 
the disease as well as factors that determine the response to treatments. Long-term, such research aims to improve the therapeutic management of patients 
with metastatic renal cell carcinoma. 
 
II 
PROJECT ORGANIZATION 
A 
STUDY PROCEDURES 
The protocol for this research provides for you to be followed for 3 years and to have a blood sample drawn at inclusion, 6 months, 12 months and during 
disease progression, if it occurs. 
These blood samples are collected in order to assay certain substances the presence of which might be linked to attaining complete remission or to the 
appearance of a recurrence (these substances are called "biological and genetic markers"). Apart from these blood samples, this research does not affect the 
treatment of your disease. 
Your participation in this study will involve: 
• 
Authorizing the physician to collect personal data about the characteristics of your cancer, the treatments received to date and your possible 
associated diseases. 
• 
Authorizing the physician to request the sending and the preservation of your histological sample made before the initiation of sunitinib. 
• 
Having a blood sample collected of approximately 2 x 5 ml for identification of biological and genetic markers present during your inclusion in the 
study. Your blood sample will be labeled anonymously. 
• 
Having a blood sample collected of approximately 2 x 5 ml for identification of biological and genetic markers present during your 6-month and 12-
month visits. Your blood sample will be labeled anonymously. 
• 
In the event of a progression of your renal cell carcinoma, completing a second questionnaire on the characteristics of that progression as well as 
having a second blood sample of around 2 x 5 ml collected to identify the biological and genetic markers. 
• 
In the event of a complete remission of your renal cell carcinoma, completing a second questionnaire on the characteristics of the complete 
remission as well as having a second blood sample of around 2 x 5 ml collected to identify the biological and genetic markers that are predictive of 
this CR. 
As with all sample collection, these samples may cause a slight pain or cause a bruise on your arm at the collection site. 
During the research, all of the samples collected from subjects participating in the research will be sent and stored at the Institut Gustave Roussy laboratories 
(114 rue Edouard Vaillant, 94800 Villejuif, France) in order to perform the screening of biological and genetic markers. The storage of this biological material will 
be the responsibility of the directors of those laboratories. 
The biological and genetic samples collected will be used exclusively for the research. 
By accepting to participate in this study, you also consent to the future use of these samples for anything that concerns the objective of the study. Indeed, new 
markers will probably be identified as scientific knowledge advances. 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
Patient information leaflet and informed consent 
form 
Page:  
35 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 36 of 172 
 
B 
PLANNED DURATION OF THE STUDY AND PLANNED NUMBER OF PATIENTS 
If you decide to participate in this study, you will be one of 80 subjects with metastatic renal cell carcinoma treated with SUTENT® and included by 5 of the 
participating sites l’Institut Gustave Roussy de Villejuif, l’Hôpital Européen Georges Pompidou de Paris, l’Hôpital Civil de Strasbourg,  l’Institut 
Calmette de Marseille and l’hôpital Nord de Marseille. 
The maximum duration of your participating in this study will be 3 years (36 months). 
This study will not change your relationship with your physician, who may prescribe any procedure during this consultation, if he deems it to be necessary. 
 
C 
RESTRICTIONS ASSOCIATED WITH THE STUDY AND INFORMATION FOR THE PATIENT 
This study does not have any restrictions that you need to observe. 
Should the study result in any harm to you, in compliance with current French law, you will be covered during the entire study by insurance taken out by the 
sponsor Pfizer. 
Contact details of the person to contact for additional information or in case of injury related to the study: 
______________________ 
______________________ 
III 
RESPONSABILITIES, PATIENT'S RIGHTS AND CONFIDENTIALITY 
A 
WITHDRAWAL FROM STUDY 
The participating physician, i.e. the physician who suggests this study to you, or the sponsor may decide to discontinue your participation in this study, if: 
a) 
You do not follow the participating physician's instructions 
b) 
You develop a serious condition that would require discontinuation of treatment 
c) 
The study is stopped by the sponsor or the health authorities 
B 
RIGHTS 
Your participation in this study is voluntary and entirely of your own free will. Please take the time to read this information leaflet and discuss it with your 
physician and your family, if you wish. Do not hesitate to ask your physician any questions if you require further information. If you decide not to participate or 
withdraw from the study for any reason whatsoever, this shall not affect your relationship with the physician who is monitoring you as part of this study, or with 
your attending physician. If you change your mind and decide not to participate in this supplementary study, you can ask for the destruction of your samples by 
approaching the study physician. The samples will then be destroyed. 
If you have any questions during the course of the study, you should contact the physician monitoring you as part of this study. 
Pursuant to French law, the protocol describing the study in which you are participating received a favorable opinion from the CCTIRS - Comité Consultatif sur 
le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (French Advisory Committee for Data Processing in Health Research) on 
18/01/2012. The committee is charged with verifying the scientific relevance of the trial, the conditions required for your protection and the upholding of your 
rights. 
The drawing of blood samples was the subject of a prior declaration by the competent authority [ANSM - Agence Nationale de Sécurité du Médicament (The 
French National Agency for Medicines and Health Products Safety)]. 
If you want, your attending physician will be informed about your participation in this study. 
Following analysis of the data for all patients, you will be informed of the overall results of this study via the physician monitoring you as part of this study. 
 
 Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials
 
Patient information leaflet and informed consent 
form 
Page:  
2 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
Pfizer Confidential 
Page 37 of 172 
 
 
C 
DATA CONFIDENTIALITY 
All medical records and documentation from this study that identify you will be kept strictly confidential and will not be subject to any disclosure to third parties, to 
the extent permitted by French laws and/or regulations currently in force. The data gathered regarding you that are identified by a code number will remain 
anonymous for the future analysis of study results. If the overall results from this study are likely to be communicated or published in the medical literature, only 
anonymized data will be presented. 
In the context of the present study, you accept that designated representatives of the health authorities, representatives of Pfizer, other physicians, nurses and 
people participating in this study will have access to medical records about you. You agree that these documents shall be communicated under the conditions 
described above, even if you decide to withdraw from this study. 
Data about you recorded during this study for epidemiological evaluation, including data about your lifestyle, will be subject to computer processing by or on 
behalf of Pfizer. In accordance with French law no. 78-17 of January 6, 1978 on data protection, as amended by French law no. 2004-801 of August 6, 2004 on 
the protection of individuals with regard to treatment of personal data, you may exercise your rights of access to and rectification of your data. You can exercise 
those rights at any time by contacting the physician monitoring you as part of the study. 
Pfizer owns the data, will control their use and will take all necessary measures to ensure their protection. 
IV 
PARTICIPATING PHYSICIAN'S COMPENSATION 
The participating physician receives financial compensation from the sponsor for this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
Patient information leaflet and informed consent 
form 
Page:  
3 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 38 of 172 
 
I 
CONSENT FORM FOR PARTICIPATION IN THE STUDY 
 
Dr  ...........................................  invited me to participate in a study conducted by Pfizer on the treatment of metastatic renal cell carcinoma entitled: "A PROSPECTIVE 
STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA" 
I have reached the age of majority. 
I belong to a social security scheme or am a beneficiary of such a scheme. 
I have read the information above and have fully understood it. I was given the time and opportunity to ask any questions I wanted to about the study and this form. I have 
read all pages of this consent form and have understood the risks and benefits described. 
I have been informed that I will be covered by insurance taken out by the sponsor, Pfizer, pursuant to current French legislation. 
I understand that data concerning me will remain strictly confidential. I consent to them being consulted only by members of Pfizer, their representatives, any service 
providers under contract to Pfizer and by the various regulatory authorities, provided that Pfizer is committed to respecting the confidentiality of the data pursuant to law 
no. 78-17 of January 6, 1978. 
I accept that the data recorded during this study will be subject to computerization by Pfizer or on its behalf. I understand that my right of access and of rectification, as 
provided by law no. 78-16 of January 6, 1978 relating to data processing, data files and individual liberties, as amended by law no. 2004-801 of August 6, 2004 relating to 
the protection of individuals with regard to the processing of personal data, may be exercised at any time from Pfizer via the physician monitoring me during this study. 
It was explained to me that I am free to accept or refuse to participate in this study and to withdraw from the study at any time without this changing my relationship with 
my physician. Signature of this consent form does not discharge Pfizer from its responsibilities and I retain all my rights as guaranteed by law. 
I agree that the results of the study may be published and communicated to the authorities concerned and to Pfizer. I freely agree to participate in this study under the 
conditions specified in this document. 
By signing this consent form I confirm that all of the information I have provided, particularly concerning my medical history, is accurate to the best of my knowledge. 
I understand that I will be given a copy of this signed consent form. 
 
The patient 
Surname / First name in capital letters: 
___________________________________ 
Date: ---------------------------- 
Patient's signature: 
The participating physician 
Surname / First name of participating physician in capital letters: 
Dr / Prof: ----------------------------------------------------------------------------------------------- 
Date: ---------------------------------------------------------------------------   
Participating physician's signature: 
 
Sponsor: 
PFIZER 
 
23-25, avenue du Dr Lannelongue  
 
75668 PARIS Cedex 14, France 
 
 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
Patient information leaflet and informed consent 
form 
Page:  
4 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

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Part II 
Study title: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL CELL 
CARCINOMA 
Use and storage of blood samples for exploratory research 
Investigator's name: 
Telephone number 
Name of patient: 
Part I of this consent form describes the main part of the biomedical research on SUTENT®. 
Part II below requires your consent in order to be able to use a blood and histological sample to study your genes, also called DNA.and cellular 
markers. 
However, if you do not want to provide these additional samples, you can still participate in the main study described in Part I of the consent form. 
WHAT IS THE PURPOSE OF THIS RESEARCH? 
Blood contains genes. The genes provide instructions that govern different processes taking place in the body and physical characteristics such as eye 
color. Genes differ slightly from one person to another. Information on these differences between individuals allows researchers to learn more about 
diseases, the best way to treat them and to understand how each one responds to medication. 
 
 
 
 
 
 
 
 
 
 

The objective of this study is to collect, store and use your blood sample to study the genes, RNA, proteins and metabolites. Your sample will be studied 
only with reference to the following: 
x Analysis of genetic polymorphisms of VEGF-A (SNPs) in patients receiving Sunitinib in CR (cases) and selected as controls. 
x To determine whether this polymorphism correlates with complete remission or progression. 
x To determine whether polymorphisms of VEGF can reduce the response rate of patients receiving Sunitinib.  
 
 
 
 
 
 
 
 
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Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 40 of 172 
This research could contribute to developing new treatments or improving existing treatments. The sample will be stored until it is used up or destroyed 
at Pfizer's discretion of, which may take several years. The information obtained following its analysis will be saved indefinitely. This will allow 
researchers to continue their investigations on genes in the future that have not yet been discovered today. 
No genetic research in addition to the objectives described above will be carried out. 
The samples will be stored by the Institut Gustave Roussy (IGR), 114 rue Edouard Vaillant, 94800 Villejuif, France.  
Pursuant to current French legislation: 
• The protocol describing this research: 
o Has received a favorable opinion from CCTIRS - Comité Consultatif sur le Traitement de l’Information en matière de 
Recherche dans le domaine de la Santé (French Advisory Committee for Data Processing in Health Research). 
o Has been declared to the competent authority [ANSM - Agence Nationale de Sécurité du Médicament (The French National 
Agency for Medicines and Health Products Safety)]. 
• Pfizer has taken out civil liability insurance covering any health problems in connection with your participation in this research. 
WHAT WILL HAPPEN IF I PARTICIPATE IN THIS RESEARCH? 
If you participate in this research, analysis will be performed on samples taken in the context of this observational study. 
- 
VGEF-A (SNPs) polymorphisms genetic 
- 
Cellular markers 
WHAT ARE THE BENEFITS ASSOCIATED WITH MY PARTICIPATION? 
You are not expected to benefit from your participation in this supplementary research. On the other hand, the knowledge acquired thanks to this 
research may benefit other people. 
WILL MY DATA BE CONFIDENTIAL? 
As described in Part I, all data will remain strictly confidential and anonymized. The results of this part of the study are liable to be published for 
scientific purposes, but under no circumstances will your identity be revealed. Consequently, neither you nor any other person will be able to obtain the 
results of any genetic analysis performed on your sample. 
Before being relabeled, your sample will be treated as "sensitive personal data". 
By participating in this study, you agree that (1) the research team, (2) Pfizer's representatives and authorized companies, (3) the EC that approved this 
study and (4) national and international regulatory authorities can have access to and examine your medical records in order to (a) conduct the study, 
(b) check the accuracy of the data, (c) monitor that it is being conducted in accordance with good clinical practice and the law and (d) conduct other 
research associated with the study. 
WHO WILL HAVE OWNERSHIP OF MY SAMPLE(S)? 
Pfizer will ensure that the samples are used in accordance with the objectives of this supplementary study, the associated informed consent form and 
the ethical approval received. 
The study sponsor will not sell or transfer ownership of the sample to any third parties. The samples will only be used by Pfizer and/or researchers 
working with Pfizer, and only as part of the research study described above. Pfizer may use information from your sample in order to develop products 
or procedures from which it may make a profit. Pfizer intends to retain the exclusive rights to any products and processes that are developed using 
information from your sample. You will not receive any payments for products of any kind that are developed thanks to this research. 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
Patient information leaflet and informed consent 
form 
Page:  
6 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 41 of 172 
 
 
 
WHAT WILL HAPPEN IF I DECIDE TO NO LONGER PARTICIPATE IN THE STUDY? 
If you change your mind and decide not to participate in this supplementary study, you can ask for the destruction of your samples by approaching the 
study physician (in this case, they will be destroyed). However, once your identity no longer appears on the sample (during the analyses), it will no 
longer be possible to have it destroyed. 
Your participation in this biomedical research is voluntary and entirely of your own free will. If you decide not to participate in it or you withdraw from this 
research for any reason whatsoever, you will continue to receive the same advantages that you were able to before. This will in no way affect your 
relationship with the physician monitoring you as part of this research, as well as with your attending physician. If you so wish, you may be given time to 
reflect. 
If you decide to withdraw from this research, you must inform the study physician. In the absence of this information from you, s/he will be required to 
contact you again in order to confirm your decision. If you withdraw from the study, no new information concerning you will be collected, however 
information that has already been collected may be used. 
 
MY CONTACT DETAILS 
Consenting to this supplementary part of the study is completely optional and separate from the consent given to participation in the clinical study on the 
medicinal product (Part I). 
Before deciding to participate in this part of the study, you will be given time to study the information contained in this form. If you have any questions 
regarding this research and/or your rights, please contact: 
 
NAME OF PHYSICIAN TO CONTACT 
Telephone number 
Dr / Prof: 
Tel.:  
Email: 
 
 
 
 
 
 
 
 
 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
 
 
 
Patient information leaflet and informed consent 
form 
Page:  
7 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 42 of 172 
CONSENT FORM FOR PARTICIPATION IN THE STUDY 
Study title: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL CELL 
CARCINOMA 
Dr  Invited me to participate in a biomedical study organized by Pfizer. 
This consent form relates to the supplementary pharmacogenomics study to 
describe the characteristics of patients with mRCC and presenting CR (Cases) 
with Sunitinib and to compare them with the characteristics of patients with 
mRCC and not presenting CR (Controls) with Sunitinib in order to identify 
factors associated with the occurrence of complete remission. 
I have understood the information above. I was given the time and opportunity 
to ask any questions I wanted to about the research and this form and all of 
my questions were answered. 
It was explained to me that I am free to accept or refuse to participate in this 
study and to withdraw from the study at any time without this changing my 
relationship with my physician. 
Signature of this consent form does not discharge Pfizer from its 
responsibilities and I retain all my rights as guaranteed by law. 
By signing this consent form, I confirm that: 
• 
I have reached the age of majority 
• 
I belong to a social security scheme or am a beneficiary of such a 
scheme. 
I was informed that: 
• 
I will be covered during this biomedical research by the insurance taken 
out by Pfizer. 
• 
Data pertaining to me will remain strictly confidential. I authorize access 
to the data to Pfizer, its representatives, any service provider under 
contract to Pfizer and the various regulatory authorities. 
I accept that: 
• 
The data recorded during this research will be subject to computerization 
by Pfizer or on its behalf. I understand that I may exercise my right of 
access and rectification from Pfizer at any time via the physician 
monitoring me for this research. 
• 
The data will be collected, used and transferred in accordance with the 
conditions described. 
 
I therefore freely agree to participate in this biomedical research under the conditions specified in this document and a signed copy of this patient information 
leaflet and informed consent form will be returned to me. 
 
Protocol A6181209 
Patient information leaflet and consent form for patients with mRCC selected as controls and treated with Sunitinib 
Version dated April 11, 2016 
Patient's initials 
 
 
Patient information leaflet and informed consent 
form 
Page:  
8 of 8 
PATIENT WITH MRCC AND TREATED WITH SUTENT - CONTROLS 
 
Protocol no.: A6181209 
Date: 11/04/2016 
Location 
Language: French 
Site no.: All sites 
Country: France 
Protocol title: APERCU study: PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED WITH SUNITINIB IN 
PATIENTS WITH METASTATIC RENAL CELL CARCINOMA 
Name of participating physician 
Telephone number 
Name of patient 
The patient (Surname / First name of patient in capital letters) 
The participating physician (Surname / First name of participating physician in 
capital letters) 
----------------------------------------------------------------------------- 
Dr / Prof ------------------------------------------------------------------------- 
Patient's signature: 
Date: ------------------------- 
Participating physician's signature: 
Date: ------------------------- 
The impartial witness * / legal guardian / family member ** / 
trusted person ** / guardianship judge 
* Impartial witness: a person who actually attended an event and can validly attest to 
this. S/he has no personal interest in the patient's consenting and is totally 
independent of the investigator and of the sponsor. 
** Trusted person / Family member: person, freely chosen by the patient from 
his/her circle of family and friends and in whom s/he has complete confidence 
independent of the context of the clinical trial and who cannot be unfairly influenced. 
This person assists with informing the patient and with the obtaining of the informed 
consent if the patient or his/her legal guardian are unable to read. S/he reads the 
informed consent form and all other written information given to the patient. 
* & ** pursuant to the articles of the French Public Health Code: article L 1122-1-1 
and article L 1111-6 
__________________________________________ 
Surname / First name in capital letters 
_______________________  
_____________ 
Signature  
Date 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 43 of 89 
 
13.5. Appendix 5: Case report form for patients with mRCC in complete remission (Cases) 
 
CASE REPORT FORM 
 
PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED 
WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL CELL 
CARCINOMA (mRCC) 
 
Cross-sectional then longitudinal, descriptive, multicenter, prospective study with 3-year patient 
follow-up and compilation of a biobank 
 
APERÇU protocol 
Identification no.: A6181209 
 
Favorable opinion from CCTIRS on 18/01/2012 
 
Patient code 
 
Site no.: 
Patient number, 
allocated by the 
site 
 
Investigator: 
Dr______________________________________ 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 44 of 89 
 
 
CR SCREENING VISIT 
Patient code: |___|___||___|___|___|  
Consent form signature date 
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Screening visit date 
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 
INCLUSION CRITERIA : 
 
 
1. 
Adult patients (≥ 18 years) 
2. 
Patients with mRCC confirmed by histological analysis 
3. 
Treated with Sunitinib according to a regimen in the text of the SmPC 
4. 
Presenting a complete remission in the preceding 5 years (according to 
RECIST v1.1) with Sunitinib only or combined with localized treatment 
(surgery, radiotherapy, cryoablation or radiofrequency ablation) 
5. 
Patients of childbearing age using a mandatory method of contraception 
6. 
Affiliated to a social security scheme 
7. 
Informed about the study methods and having given their consent 
 
 
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
EXCLUSION CRITERIA 
 
8. 
Complete remission occurring in the absence of treatment with Sunitinib 
 
YES 
 
 
NO 
 
 
Date of birth (mm/yyyy): |___|___| |___|___|___|___| 
Date of diagnosis of initial renal cancer |___|___| |___|___| |_2_|_0_|_ _|___| (dd/mm/yyyy) 
Date of diagnosis of metastatic renal cell carcinoma |___|___| |___|___| |_2_|_0_|_ _|___| 
(dd/mm/yyyy) 
SUNITINIB start date |___|___| |___|___| |_2_|_0_|__|___| (dd/mm/yyyy)  
Metastatic sites at start of SUNITINIB 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
(please specify): ……………………….. 
 
YES 
NO 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 45 of 89 
 
NUMBER OF METASTATIC SITES: |___| 
CR date |___|___| |___|___| |_2_|_0_|__|___| (dd/mm/yyyy) 
 
 Complete remission obtained by: 
YES 
NO 
- Medical treatment only 
  
 
- Combined with localized treatment 
  
 
If yes: 
o Surgery 
 
 
Site:  .......................................... 
o Radiotherapy 
 
 
Site:  .......................................... 
o Radiofrequency 
 
 
Site:  .......................................... 
o Cryoablation 
 
 
Site:  .......................................... 
o Metastasectomy 
 
 
Site:  .......................................... 
o Other 
 
 
Site:  .......................................... 
 
Radiological assessment of the complete remission (RECIST v 1.1 criteria) 
- Disappearance of target lesions 
- All target or non-target lymph nodes < 10 mm 
- Disappearance of non-target lesions 
- Absence of new lesions 
YES 
NO 
  
 
  
 
  
 
  
 
 
SAMPLING DURING SCREENING VISIT 
YES 
NO 
- 
Blood sample of 2 times 5 ml 
  
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Histological sample of primitive tumor 
  
 
Sampling date |
|
| |
|
| | 2 | 0 | 1 |
| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 46 of 89 
 
 
INCLUSION 
 
DEMOGRAPHIC DATA 
Consultation date 
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
DEMOGRAPHIC DATA 
Age 
|___|___| years 
Sex 
 Male 
 Female 
Height (cm) 
|___|___|___| 
Weight (kg) 
|___|___|___|. |___| 
 
DATA RELATING TO THE STATUS OF A PATIENT IN COMPLETE REMISSION 
AT START OF SUNITINIB 
Date of initial diagnosis of renal carcinoma 
|___|___| |___|___| |_2_|_0_|__|___| (dd/mm/yyyy) 
Date of initial diagnosis of metastatic renal cell carcinoma  
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
NEPHRECTOMY 
Nephrectomy 
 YES 
 NO 
If 
yes, 
date 
|___|___| 
|___|___| 
|_2_|_0_|_1_|___| 
(dd/mm/yyyy) 
• 
Type of nephrectomy: 
 radical 
 partial 
 with adrenalectomy 
 without adrenalectomy 
 with lymphadenectomy 
 without lymphadenectomy 
 open 
 laparoscopic 
HISTOLOGY 
• 
Pathoanatomic classification: 
YES 
NO 
- Clear cell carcinoma 
  
 
- Papillary cell carcinoma 
  
 
- Chromophobe cell carcinoma 
  
 
- Bellini's collecting duct carcinoma 
  
 
- Medullary cell carcinoma 
  
 
- Sarcomatoid contingent 
  
 
- Other 
(please specify):  ..................................................................... 
• 
TNM classification: T |___| N |___| M |___| 
• 
Fuhrman nuclear grade: I |___| II |___| III |___| IV |___| 
YES 
NO 
• 
Presence of necrosis? 
  
 
•
Vascular embolism



Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 47 of 89 
 
DATA RELATING TO THE STATUS OF A PATIENT IN COMPLETE REMISSION 
AT START OF SUNITINIB 
Sunitinib start date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): .................................................................. 
NUMBER OF METASTATIC SITES: |___| 
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MSKCC PROGNOSTIC CLASSIFICATION 
 Good prognosis (0 pejorative factors) 
 Moderate diagnosis (1 or 2 pejorative factors)  
 Good diagnosis (more than 2 pejorative factors) 
DATA RELATING TO COMPLETE REMISSION 
Complete remission date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
• 
Complete remission obtained by: 
YES 
NO 
- Medical treatment only 
  
 
- Combined with localized treatment 
  
 
If yes: 
o Surgery 
 
 
Site:  ............................................... 
o Radiotherapy 
 
 
Site:  ............................................... 
o Radiofrequency 
 
 
Site:  ................................................ 
o Cryoablation 
 
 
Site:  ............................................... 
o Metastasectomy 
 
 
Site:  ............................................... 
o Other 
 
 
Site:  ............................................... 
RADIOLOGICAL ASSESSMENT OF THE COMPLETE REMISSION (RECIST v 1.1 criteria)  
 
YES 
NO 
- Disappearance of all known target lesions 
  
 
- Disappearance of all non-target lesions 
  
 
- No appearance of new lesions 
  
 
- All target or non-target lymph nodes < 10 mm 
  
 
TREATMENT STRATEGY FOLLOWING COMPLETE REMISSION 
 
YES 
NO 
- Continuation of Sunitinib treatment 
  
 
- Discontinuation of Sunitinib treatment 
  
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 48 of 89 
 
 SAMPLING BEFORE START OF SUNITINIB 
* A delay of 6 weeks is tolerated between initiation and sampling 
YES 
NO 
- 
Blood sample of 2 times 5 ml 
  
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Histological sample of primitive tumor 
  
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 49 of 89 
 
ANNUAL VISIT FOLLOWING A CR  
 
 
Visit date 
|___|___| |___|___| |_2_|_0_|_1_|___| (jjmmaaaa) 
If a Sunitinib complementary treatment (pseudo adjuvant) is realised since the CR, could you 
indicate the duration |___|___| (month)  
 
Disease State  
 
• Desease evolution :   
 - Complete Response 
 
 
 
 
 
  - Partial Respsonse
 
  
- Progression 
 (Thanks to complete the disease 
progression  
follow-up visit) 
 
- Stabilisation 
 
 
- No evaluated 
 
 
Modification treatmentt.  
• Sunitinib treatment always on going :  
 
 Actual dosage; |___|___| ,  |___|___|  mg  / j  
Actual schema :   
4/2  
  
 
 
  
 
 
2 /1   
 
 
 
  
 
 
Continuous 
 
 
 
  
 
 
Other  
 
• Sunitinib temporary cessation: 
Sunitinib temporary cessation duration |___|___| (days) 
 
 Sunitinib cessation date: |___|___| |___|___| |_2_|_0_|_ _|___| (jjmmaaaa) 
 
Temporary cessation Reason: 
Progression  
 
 
 
 
 
 
 
Intolérance  
 (Thanks to complete Adverse Event 
form) 
 
 
 
 
 
 
Complete Response 
 
 
 
 
 
 
 
Local treatment 
  
 
 
 
 
 
 
Other 
…………………………………………………… 
Has the sunitinib been taken back? Yes  
 No   
 
 
 
If yes, Sunitinib recovery date |___|___| |___|___| |_2_|_0_|_ _|___| (jjmmaaaa) 
 
Définitive Cessation  
Sunitinib cessation date : |___|___| |___|___| |_2_|_0_|_ _|___| (jjmmaaaa) 
Cessation reason : 
Progression  
 
 
 
 
Intolerance  
 (Thanks to complete Adverse Event form) 
 
 
 
Complete Response Retention  
 
 
 
 
Doctor / Patient choice          
 
 
 
 
Other 
 …………………………………………………………… 
 
 
 
 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 50 of 89 
 
 
 
 
 
DISEASE PROGRESSION VISIT  
FOLLOWING A CR 
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
If additional treatment with Sunitinib was given after the complete remission (pseudo-adjuvant), could 
you please indicate the duration |___|___| (months) 
LOCALIZED OR DISTANT PROGRESSION 
LOCAL PROGRESSION 
YES  
NO  
DISTANT PROGRESSION 
YES  
NO  
If yes: 
Progression at a known metastatic site  
 
 
 
New metastatic site 
Yes 
No  
Yes 
No  
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): ................................................................... 
NUMBER OF METASTATIC SITES |
|
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BLOOD SAMPLING DURING PROGRESSION 
 
YES 
NO 
- Blood sample of 2 times 5 ml 
 
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 51 of 89 
 
 
 
studyS OF SYSTEMIC TREATMENT OF THE PROGRESSION 
Route of 
administration 
Duration of 
administration 
Daily dosage 
Anti-VEGF 
- 
Bevacizumab (with interferon) ...........  
- 
Bevacizumab (without interferon) ......  
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
Tyrosine kinase inhibitor 
- 
Restart of Sunitinib .............................  
- 
Sorafenib .............................................  
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
mTOR inhibitor 
- 
Temsirolimus ......................................  
- 
Everolimus ..........................................  
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
Other systemic treatment (please specify) 
.......................................................................... 
.......................................................................... 
.......................................................................... 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
…………………… 
SURGICAL TREATMENT 
Please specify: 
..................................................................................................................................................................  
..................................................................................................................................................................  
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 52 of 89 
 
 
DATA RELATING TO THE END OF STUDY VISIT 
(36 months) 
To be completed only if visit took place, 
if not, complete the latest information or death form 
Did the patient attend a visit at 36 months YES  
NO  
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Best objective response observed since progression 
- Complete  
- Partial  
- Progression  
- Stable  
Duration of administration of the progression treatment |___|___| (months) 
LATEST INFORMATION OR DEATH FROM 
LATEST INFORMATION 
Did the patient withdrawn from study prematurely? 
YES
NO  
Latest information date: |
|
| |
|
| | 2 | 0 | 1 |
| (dd/mm/yyyy)
 
- Complete remission persisting since the inclusion visit 
- Complete remission after treatment of the recurrence 
- Disease progression 
 
 
Number of lines of treatment received after progression, post CR: 
YES 
 
 
 
NO 
 
 
 
DEATH 
 YES 
NO 
Date of death: |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 53 of 89 
 
 
13.6. Appendix 6: Case report form for patients with mRCC NOT in complete remission 
(Controls) 
 
CASE REPORT FORM 
 
 
PROSPECTIVE STUDY OF COMPLETE REMISSIONS OBSERVED 
WITH SUNITINIB IN PATIENTS WITH METASTATIC RENAL CELL 
CARCINOMA (mRCC) 
 
Cross-sectional then longitudinal, descriptive, multicenter, prospective study with 3-year patient 
follow-up and compilation of a biobank 
 
APERÇU protocol 
Identification no.: A6181209 
 
Favorable opinion from CCTIRS on 18/01/2012 
 
 
Patient code 
 
Site no.: 
Patient number, 
allocated by the 
site 
 
 
Investigator: 
Dr______________________________________ 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 54 of 89 
 
 
INCLUSION 
 
 
Consent form signature date 
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Consultation date 
|___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 
DEMOGRAPHIC DATA 
 
Date of birth (mm/yyyy)  
|___|___| |___|___|___|___| 
Age 
|___|___| years 
Sex 
Male 
Female 
Height (cm) 
|___|___|___| 
Weight (kg) 
|___|___|___|. |___| 
 
INCLUSION CRITERIA : 
 
 
1. Adult patients (18 years) 
2. Life expectancy ≥ 3 months 
3. Patients with mRCC confirmed by histological analysis 
4. No previous treatment with Sunitinib 
5. Patients for whom the indication of Sutent® is retained in compliance 
with the text in the SmPC 
6. Platelets  100 x 109/l, hemoglobin > 9 g/dl, neutrophils >1.5 x 109/l 
7. Bilirubin < 2 mg/dl, aspartate transaminase (AST) and alanine 
transaminase (ALT)  2.5 times upper limit of normal or  5 times upper 
limit of normal in the presence of hepatic metastases 
8. Patients of childbearing age must use a method of contraception 
9. Affiliated to a social security scheme 
10. Informed about the study methods and having given their consent 
 
 
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EXCLUSION CRITERIA 
 
11. Previous systemic treatment 
YES 
 
NO 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 55 of 89 
 
12. Patients who are pregnant or breastfeeding 
13. Any contraindications to Sunitinib in accordance with the text in the 
SmPC 
 
 
 
 
 
 
 
INITIAL TREATMENT OF PATIENT WITH METASTATIC RENAL CELL 
Date of initial diagnosis of renal carcinoma 
|___|___| |___|___| |_2_|_0_|__|___| (dd/mm/yyyy) 
Date of initial diagnosis of metastatic renal cell carcinoma (date of initial discovery of the first 
metastases) |__|__| |__|__| |_2_|_0_|_ _|___| (dd/mm/yyyy) 
Sunitinib treatment start date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
NEPHRECTOMY 
Nephrectomy 
 YES 
 NO 
If yes, date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
• 
Type of nephrectomy: 
 radical 
 partial 
 with adrenalectomy 
 without adrenalectomy 
 with lymphadenectomy 
 without lymphadenectomy 
 open 
 laparoscopic 
 
HISTOLOGY 
• 
Pathoanatomic classification: 
YES 
NO 
- Clear cell carcinoma 
  
 
- Multilocular cystic clear cell carcinoma 
  
 
- Papillary cell carcinoma 
  
 
- Chromophobe cell carcinoma 
  
 
- Bellini's collecting duct carcinoma 
  
 
- Medullary cell carcinoma 
  
 
- Sarcomatoid contingent 
  
 
- Other(please specify):………………………………………… 
  
 
• 
Tumor size |___|___|___| mm 
• 
TNM classification: T |___| N |___| M |___| 
• 
Fuhrman nuclear grade: I |___| II |___| III |___| IV |___| 
YES 
NO 
• 
Presence of necrosis? 
  
 
• 
Vascular embolism 
  
 
• 
Sarcomatoïdis composante 
  
 
 
BLOOD SAMPLING BEFORE START OF SUNITINIB 
* A delay of 6 weeks is tolerated between initiation and sampling 
YES 
NO 
- 
Blood sample of 2 times 5 ml 
  
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 56 of 89 
 
Histological sample of primitive tumor 
  
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 
 
 
 
DATA RELATING TO THE STATUS OF A PATIENT WITH mRCC BEFORE START 
OF SUNITINIB 
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): .................................................................. 
NUMBER OF METASTATIC SITES: |
|
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MSKCC PROGNOSTIC CLASSIFICATION 
 Good prognosis (0 pejorative factors) 
 Moderate diagnosis (1 or 2 pejorative factors)  
 Good diagnosis (more than 2 pejorative factors) 
 
DATA RELATING TO PATIENTS WITH mRCC AFTER 6 MONTHS OF 
TREATMENT WITH SUNITINIB 
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Sunitinib Actual dose 
50mg 
37,5mg 
25mg 
Actual schema  
 4/2  
2/1  
 Continu 
CLINICAL ASSESSMENT ACCORDING TO RECIST v 1.1 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 57 of 89 
 
Partial response 
Yes   
No  
Percentage tumor reduction:  ............................... % 
Complete response 
Yes   
No  
If yes, the patient should move to the arm of patients in CR 
Stable disease 
Yes  
No  
Progression 
Yes 
No  
If yes: Progression at a known metastatic site 
Yes  
No  
 
New metastatic site 
Yes  
No  

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 58 of 89 
 
 
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): .................................................................. 
NUMBER OF METASTATIC SITES |
|
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BLOOD SAMPLING AT 6 MONTHS 
YES 
NO 
- 
Blood sample of 2 times 5 ml 
 
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 59 of 89 
 
 
DATA RELATING TO PATIENTS WITH mRCC AFTER 12 MONTHS OF 
TREATMENT WITH SUNITINIB 
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Sunitinib Actual dose 
50mg 
37,5mg 
25mg 
Actual schema  
 4/2  
2/1  
 Continu 
CLINICAL ASSESSMENT ACCORDING TO RECIST v 1.1 
Partial response 
Yes   
No  
Percentage tumor reduction:  ............................... % 
Complete response 
Yes   
No  
If yes, the patient should move to the arm of patients in CR 
Stable disease 
Yes  
No  
Progression 
Yes  
No  
If yes: Date of progression |__|__| |__|__| |_2_|_0_|__|__| (dd/mm/yyyy) 
If yes: Progression at a known metastatic site 
Yes  
No  
 
New metastatic site 
Yes  
No  
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): .................................................................. 
NUMBER OF METASTATIC SITES: |
|
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BLOOD SAMPLING AT 12 MONTHS 
YES 
NO 
- Blood sample of 2 times 5 ml 
 
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 60 of 89 
 
 
DATA RELATING TO PATIENTS WITH mRCC DURING DISEASE 
PROGRESSION 
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
CLINICAL ASSESSMENT ACCORDING TO RECIST v 1.1 
Date of disease progression |___|___| |___|___| |_2_|_0_|_1_|___| 
(dd/mm/yyyy) 
Progression at a known metastatic site 
Yes  No  
New metastatic site
Yes No 
METASTATIC SITES 
LOCALIZATION OF METASTASES 
- Lungs 
- Bone 
- Liver 
- Adrenal glands 
- Pancreas 
- Brain 
- Lymph nodes 
o Supradiaphragmatic 
o Infradiaphragmatic 
- Recurrence at the nephrectomy renal bed 
- Other 
 
(please specify): .................................................................. 
NUMBER OF METASTATIC SITES: |___| 
YES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BLOOD SAMPLING DURING PROGRESSION 
YES 
NO 
- 
Blood sample of 2 times 5 ml 
 
 
Sampling date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 61 of 89 
 
 
Data relating to the end of study visit of patients NOT in CR 
(36 months) 
Did the patient attend a visit at 36 months 
YES NO  
Visit date |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
Is the patient still being treated with Sunitinib? YES 
NO   
If yes, is the patient presenting a: 
PARTIAL RESPONSE 
YES   
NO  
COMPLETE RESPONSE 
YES   
NO  
STABLE DISEASE 
YES  
NO  
PROGRESSION 
YES  
NO  
If no, is the patient presenting  
disease PROGRESSION 
YES  
NO  
Please specify the new treatment: ............................................................  
Sunitinib discontinuation date |___|___| |___|___| |_2_|_0_|_1_|___| 
Number of previous lines of treatment………… 
 
LATEST INFORMATION 
Did the patient withdraw from study prematurely? YES 
NO  
Latest information date: |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 
DEATH 
YES  
 NO  
Date of death: |___|___| |___|___| |_2_|_0_|_1_|___| (dd/mm/yyyy) 
 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 62 of 89 
 
 
13.7. Appendix 7: Laboratory tests 
Conventional 
units 
Conversion 
factor 
SI units 
Hematology 
Erythrocytes 
106/mm3 
x 106 
1012/l 
Hemoglobin (Hb) 
g/dl 
x 10 
g/l 
Platelet count 
103/mm3 
x 109 
1012/l 
Leukocytes 
103/mm3 
x 106 
109/l 
Leukocyte differential count 
% 
x 0.01 
fraction 
Schistocytes 
Haptoglobin 
Biochemistry 
Total bilirubin 
mg/dl 
x 17.1 
µmol/l 
Alanine aminotransferase (ALT) 
U/l 
ND 
U/l 
Aspartate aminotransferase (AST) 
U/l 
ND 
U/l 
Alkaline phosphatase 
U/l 
ND 
U/l 
Lactate dehydrogenase (LDH) 
U/l 
ND 
U/l 
Amylase 
U/l 
ND 
U/l 
Lipase 
U/l 
ND 
U/l 
Total protein 
g/dl 
x 10 
g/l 
Albumin 
g/dl 
x 10 
g/l 
Sodium 
mEq/l 
x 1.0 
mmol/l 
Potassium 
mEq/l 
x 1.0 
mmol/l 
Calcium 
mg/dl 
x 0.25 
mmol/l 
Phosphorous 
mg/dl 
x 0.323 
mmol/l 
Creatinine 
mg/dl 
x 88.4 
µmol/l 
Uric acid 
mg/dl 
x 0.059 
mmol/l 
Glucose 
mg/dl 
x 0.055 
mmol/l 
TSH 
mU/l 
ND 
mU/l 
Thyroxine T4 
ng/dl 
x 12.9 
pmol/l 
Coagulation 
Prothrombin time PT 
seconds 
ND 
seconds 
Activated partial thromboplastin time 
aPTT 
seconds 
ND 
seconds 
International normalized ratio INR 
% 
ND 
% 
Urinalysis (test strip) 
Protein 
ND 
Glucose 
ND 
Blood 
ND 
Ketones 
ND 
Albuminuria 
Creatinuria 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 63 of 89 
 
 
13.8. Appendix 8: Prognostic factors 
- ECOG performance status 
0 Fully active, able to carry on all predisease activities without restriction. 
1 Patient restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, for example, light housework or office work. 
2 Patient ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of the waking hours. 
3 Capable of only limited self-care, confined to bed or chair 50% or more of waking hours. 
4 Patient completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 Patient is dead. 
 
- Number of metastatic sites 
- Length of time interval between diagnosis and start of systemic treatment 
- Hemoglobinemia 
- LDH 
- Corrected calcium 
- Alkaline phosphatases 

Protocol A6181209 
Final N°6 amended version dated 02/25/2019 
 
Pfizer Confidential 
Page 64 of 89 
 
 
13.9. Appendix 9: RECIST v 1.1 assessment criteria 
This section presents the definition of the criteria used to determine the objective tumor response of target 
lesions. 
- Assessment of target lesions 
Complete response (CR): Disappearance of all target lesions Pathological lymph nodes (target or non-
target) must show a reduction of the short axis to a size of < 10 mm. 
Partial response (PR): Reduction of at least 30% of the sum of the diameters of the target lesions, taking 
the sum of the initial diameters as a reference. 
Disease progression (DP): Increase of at least 20% of the sum of the diameters of the target lesions, 
taking the lowest sum in the study as the reference (including the initial sum if this is the lowest sum in 
the study). In addition the relative increase of 20%, the sum must also show an absolute increase of at 
least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). 
Stable disease (SD): Absence of sufficient reduction for a PR or absence of a sufficient increase for DP, 
taking as reference the sum of the lowest diameters during the study. 
- Assessment of non-target lesions 
This section presents the definition of the criteria used to determine the tumor response of non-target 
lesions. Although some non-target lesions may actually be measurable, it is not necessary to measure 
them; they must only be assessed qualitatively at the times specified in the protocol. 
Complete response (CR): Disappearance of all non-target lesions and normalization of tumor marker 
levels. All lymph nodes must have non-pathological dimensions (minor axis < 10 mm). 
No CR/No DP: Persistence of one or more non-target lesions and/or maintenance of the level of tumor 
marker above normal limits. 
Disease progression (DP): The appearance of one or more new lesions is also regarded as progression. 

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A618 
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PFIZER CONFIDENTIAL  
 
 
  
Page 74 of 97 
 
 
13.13 Appendix 13: Sutent – product caracteristics summary 
Summaries of product characteristics are available at the following links 
 
http://base-donnees-publique.medicaments.gouv.fr/extrait.php?specid=69225978 
http://base-donnees-publique.medicaments.gouv.fr/extrait.php?specid=65283820 
http://base-donnees-publique.medicaments.gouv.fr/extrait.php?specid=63841059 
 
A printable version will be provided to participating physicians during the implementation of 
the study.

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13.14 Appendix 14: Blood markers of angiogenesis: rationale, parameters analyzed 
and guidelines Rationale 
On the one hand, angiogenesis involves a myriad of angiogenic growth factors and inhibitors 
synthesized by tumor and stromal cells and, on the other hand, endothelial cells (ECs) and their 
progenitors. The proliferation of ECs is activated by powerful stimulators, released by tumor 
cells, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). 
It is important to remember that angiogenesis and hemostasis are linked to blood clotting and to 
fibrinolysis, which directly influence tumor angiogenesis. In fact, activated platelets release 
numerous angiogenic growth factors such as VEGF, bFGF, SDF-1 and platelet-derived growth 
factors (PDGFs) and they contribute to tumor angiogenesis within a potentially prothrombotic 
tumoral microcirculation [1,2]. 
Angiogenesis markers will be assessed in order to study the role they might play in the prediction 
of renewed disease progression. 
 
 
Angiogenesis blood markers analyzed 
The plasma levels of the following angiogenic factors will be quantified by ELISA: 
- VEGF - prognostic factor of the angiogenesis pathway; target of the antiangiogenic treatment  
administered. 
- bFGF - the levels of which correlate with the prognosis of certain solid tumors and whose 
proliferative  
action on endothelial cells in inhibited in vitro by 
- SDF-1 - synthesized in response to hypoxia. It has a chemoattractive effect on endothelial 
cells  
and thus contributes to tumor angiogenesis [3]. 
- The soluble receptors of VEGF (sVEGFR1 and s VEGFR2), which reduce the angiogenic 
activity of VEGF. 
- The 3 isoforms of PDGF (-AA, -BB and -AB) act on pericytes. 
 
 
Objectives 
 
- To assess the prognostic value of plasma VEGF in a complete response and progression 
context 
- To study other angiogenesis markers as indicators of a complete tumor response to Sunitinib. 
 
 
Schedule 
 
The peripheral whole blood collected into EDTA tubes will be tested: 
FOR CASES: 
2 x 5 ml EDTA tubes will be collected during the screening visit or during the inclusion visit and 
in the event of disease progression. 
 

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FOR CONTROLS: 
2 x 5 ml EDTA tubes will be collected before starting Sunitinib, at 6 months, at 12 months and 
during disease progression with Sunitinib. 
 
Histological specimens (if available) will be tested: 
For cases and for controls: 
A histological block or 15 slides of histological sampling of the primary tumor performed before 
the screening visit. 

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Guidelines for the sampling, processing, storage and transport of blood samples. The 
assessment of blood markers of angiogenesis will be centralized at the IGR. 
 
EDTA tubes: assessment of plasma markers of angiogenesis. After 2 rounds of centrifugation at 
2000 g at 20 °C for 10 minutes, the plasma will be stored at a temperature of < -20 °C or, 
preferably, at -80 °C. 
 
Delivery address: 
Biological Resources Center 
 
Biopathology Department  
 
Institut Gustave Roussy  
 
114 rue Edouard Vaillant  
 
94805 Villejuif 
 
Telephone: +33 (0)1 42 11 42 11 
 
References 
 
1- Niedrodzik ML & Karpatkin S. Thrombin induces tumor growth, metastasis and angiogenesis: 
Evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell, 2006;10:355-362. 
2. Lev EI, Estrov Z, Aboulfatova K, et al. Potential role of activated platelets in homing of 
human endothelial progenitor cells to subendothelial matrix. Thromb Haemost, 2006;96:498-504. 
3. Jin DK, Shido K, Kopp HG, Petit I, Schmelkov SV, et al. Cytokine-mediated deployment of 
SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med, 
2006;12:557-567. 

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13.15 Appendix 15: Analysis of genetic polymorphisms  
Rationale 
The isoforms of VEGF-A are encoded by a single gene at locus 6p12. Although no 
polymorphisms have been identified in the coding regions, several allelic polymorphisms located 
in the promoter region 5' of exon 1 or in the UTR region of exon 8 may explain the variations 
between individuals in the production of VEGF (1). It has been reported that significant 
variations in the blood levels of VEGF during hypoxia or during coagulation disorders correlate 
with polymorphisms (2, 3). Given the important pathophysiological role of angiogenesis in the 
development of clear cell carcinomas, it will be interesting to see whether these polymorphisms 
correlate with the occurrence of a complete response. 
Sunitinib is an active treatment of renal cell carcinoma that acts by inhibition of the tyrosine 
kinases of VEGFR-1 and 2. Because elevated blood levels of VEGF, as well as significant 
quantities of VEGF bound to the extracellular matrix, can influence the efficacy of Sunitinib, it 
will also be interesting to examine the link between constitutional polymorphisms of VEGF and 
the occurrence of a complete response with Sunitinib. 
Due to interference with one of the strongest targets of Sunitinib, VEGFR-2, polymorphisms may 
also perturb the level of response. 
 
Polymorphisms analyzed 
The non-exhaustive list of the polymorphisms that will be analyzed includes the analysis of the 
polymorphisms of the different VEGFRs and VEGF. The analysis of polymorphisms will be 
done by DNA sequencing after PCR amplification. The assessment of polymorphisms will be 
done at the end of the study. 
Guidelines for the sampling, processing, storage and transport of blood samples. 
2 EDTA tubes containing 5 ml samples (see Appendices 10 and 12) will produce 2 pellets of 
whole blood and allow the extraction of DNA for analysis of polymorphisms. 
Delivery address: 
Biological Resources Center 
 
Institut Gustave Roussy  
 
114 rue Edouard Vaillant  
 
94805 Villejuif 
References 
1. Watson CJ, Webb NJ, Bottomley MJ, et al: Identification of polymorphisms within the 
vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein 
production. Cytokine 12:1232-5, 2000 
2. Schultz A, Lavie L, Hochberg I, et al: Interindividual heterogeneity in the hypoxic regulation 
of VEGF: significance for the development of the coronary artery collateral circulation. 
Circulation 100:54752, 1999 

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3. Webb NJ, Bottomley MJ, Watson CJ, et al: Vascular endothelial growth factor (VEGF) is 
released from platelets during blood clotting: implications for measurement of circulating VEGF 
levels in clinical disease. Clin Sci (Lond) 94:395-404, 1998