untitled h1
final version of 17/07/2018 data

During patients' usual appointments at the sites (i.e. at enrolment and at visits for tumour assessment, carried out in practice every two to three months) the following data will be collected retrospectively and/or  
| prospectively, depending on whether the patient is a "prevalent case" (started the study treatment before the   |              |           |          |           |
|-----------------------------------------------------------------------------------------------------------------|--------------|-----------|----------|-----------|
| enrolment visit) or "incident case" (started study treatment on the day of the enrolment visit):                |              |           |          |           |
| On initiation                                                                                                   | At the       | At the    |          |           |
| Before the                                                                                                      | Anticipated  |           |          |           |
| of the                                                                                                          | enrolment    | follow-up |          |           |
| treatment                                                                                                       | end of study |           |          |           |
| treatment                                                                                                       | visit        | visits    |          |           |
| Patient reference data                                                                                          |              |           |          |           |
| Compliance with inclusion and exclusion criteria                                                                | x            |           |          |           |
| Social and demographic characteristics (sex, age)                                                               | x            |           |          |           |
| Medical and treatment history                                                                                   |              |           |          |           |
| Initial diagnosis: date of diagnosis, type of tumour (localised, metastatic)  X                                 |              |           |          |           |
| Description of previous treatments: chemotherapy (type, number of                                               |              |           |          |           |
| cycles, name of treatments), somatostatin analogue, radionuclide                                                |              |           |          |           |
| therapy, interferon-alpha                                                                                       |              |           |          |           |
| Characteristics of the tumour at treatment initiation (metastases and                                           | x            |           |          |           |
| localisation, symptoms)                                                                                         |              |           |          |           |
| Clinical parameters                                                                                             |              |           |          |           |
| Comorbidities and history: renal function, diabetes, heart failure,                                             |              |           |          |           |
| coronary heart disease, history of cerebrovascular accident,                                                    |              |           |          |           |
| hypertension, hypercholesterolaemia, lung disease (asthma, COPD etc.)                                           |              |           |          |           |
| ECOG performance status (score, examination date)                                                               | x            |           |          |           |
| Status of patient (living, lost to follow-up, deceased and cause of death)                                      | x            |           |          |           |
| Study treatments                                                                                                |              |           |          |           |
| Description of the initiation of treatment: which treatment (targeted                                           |              |           |          |           |
| therapy or other treatment), date of initiation, dose and treatment                                             |              |           |          |           |
| regimen, monotherapy/combined treatment                                                                         |              |           |          |           |
| Changes to current treatment: dose changes, temporary interruption,                                             | x*           |           |          |           |
| discontinuation and reason for discontinuation                                                                  |              |           |          |           |
| New treatment line(s) since last visit: which treatment (targeted therapy                                       |              |           |          |           |
| or other treatment), date of initiation, dose and treatment regimen,                                            |              |           |          |           |
| monotherapy/combined                                                                                            | treatment,   | dose      | changes, | temporary |
| interruptions, discontinuation and reasons for discontinuation                                                  |              |           |          |           |
| Tumour assessment                                                                                               |              |           |          |           |
| Examinations performed to assess the tumour (imaging and/or histology)                                          | x            | IX        |          |           |
| Radiological and clinical responses as judged by the investigator                                               | IX           | x         |          |           |
| Safety                                                                                                          |              |           |          |           |
| Retrospective safety (adverse events that occurred prior to inclusion in                                        |              |           |          |           |
| the study) as follows:                                                                                          |              |           |          |           |
| - If the treatment ongoing at enrolment is Everolimus, adverse events                                           |              |           |          |           |
| will be recorded retrospectively:                                                                               |              |           |          |           |
| - If they are clearly related to Everolimus and occurred after it was                                           |              |           |          |           |
| started and before enrolment.                                                                                   |              |           |          |           |
| - If they are clearly related to a Pfizer product and occurred after                                            | x*           |           |          |           |
| the first treatment line was started and before enrolment.                                                      |              |           |          |           |
| - For all other treatments ongoing at enrolment (Sunitinib,                                                     |              |           |          |           |
| chemotherapy, somatostatin analogues, radionuclide therapy or                                                   |              |           |          |           |
| interferon alpha), adverse events will be recorded retrospectively:                                             |              |           |          |           |
| - If they are clearly related to a Pfizer product and occurred after                                            |              |           |          |           |
| the first treatment line was started and before enrolment.                                                      |              |           |          |           |
| Prospective safety (all adverse events observed during the study)                                               |              |           |          |           |
| *Recorded for ALL prevalent case patients                                                                       |              |           |          |           |
final version of 17/07/2018
2.1 checking eligibility criteria

| 2.1 Checking eligibility criteria                                                          |                             |      |
|--------------------------------------------------------------------------------------------|-----------------------------|------|
| INCLUSION CRITERIA                                                                         | ❏ No                        |      |
| Patient aged 18 years or over                                                              | ❏ Yes                       |      |
| Patients treated by a targeted therapy (sunitinib or everolimus) or another treatment      |                             |      |
| (chemotherapy, somatostatin analogues, interferon alpha or radionuclide therapy), as a 1*, | ❏ No                        |      |
| ❏ Yes                                                                                      |                             |      |
| 2"                                                                                         | d, 3rd or 4th line therapy. |      |
| Patients treated for:                                                                      |                             |      |
| A neuroendocrine tumour of the pancreas that is unresectable or metastatic and             | ❏ Yes                       | ❏ No |
| confirmed by histology,                                                                    |                             |      |
| Well-differentiated,                                                                       | ❏ Yes                       | ❏ No |
| With disease progression prior to initiation of treatment in the investigator's opinion    |                             |      |
| (clinical or radiological progression)                                                     | ❏ Yes                       | ❏ No |
| Patient has been informed of the study plan                                                | ❏ Yes                       | ❏ No |
| Patient has signed the informed consent form                                               | ❏ Yes                       | ❏ No |
| A "no" to any one of these criteria means that the patient is not eligible for the study   |                             |      |
| EXCLUSION CRITERIA                                                                         |                             |      |
| Patients receiving a targeted therapy (everolimus or sunitinib) that they have already     |                             |      |
| received in an earlier treatment line (patient in rechallenge)                             | ❏ Yes                       | ❏ No |
| Patients with a diagnosis of poorly differentiated neuroendocrine carcinoma or adeno-      | - Yes                       | ❏ No |
| neuroendocrine carcinoma                                                                   |                             |      |
| Patients on their fifth or higher line of systemic treatment                               | ❏ Yes                       | ❏ No |
| Patients who refuse to give consent                                                        | - Yes                       | ❏ No |
| Patients participating in a clinical trial and in an arm in which the treatment is not     | - Yes                       | ❏ No |
| validated by an MA and by the TNCD in the versions of December 2013                        |                             |      |
| Patients who have been randomised to the placebo arm in a placebo-controlled trial or      |                             |      |
| who are taking part in a double-blind clinical trial.                                      | - Yes                       | ❏ No |
| A "yes" to any one of these criteria means that the patient is not eligible for the study  |                             |      |  
| 2.2 Social and demographic characteristics   |        |
|----------------------------------------------|--------|
| Month and year of birth                      |        |
| Sex                                          | ❏ Male |
| ❏ Female                                     |        |  
final version of 17/07/2018 2.3 Characteristics of patients on initiation of the current treatment line or treatment line initiated at enrolment 2.3.1 Type of treatment ongoing or initiated at the enrolment visit (will allow checks of distribution across the groups and will point the user to the screens to be completed §2.5)
Targeted therapy
❏ No
❏ Yes
❏ everolimus lf yes:
❏ sunitinib Other treatment
❏ Chemotherapy If yes:  
❏ Capecitabine (Xeloda®)
❏ Doxorubicin (Adriamycin®)
❏ Streptozocin (Zanosar®) ❏ Temolozomide (Temodal®)
❏ Dacarbazine (Deticene®)
❏ Oxaliplatin (Eloxatin®)
❏ Gemcitabine (Gemzar®)
❏ Cisplatin ❏ VP-16 ❏ Other, please state:
❏ Somatostatin analogues
❏ Octreotide
❏ Lanreotide
❏ Interferon alpha
❏ Radionuclide therapy Anti-secretory drugs since initiation of the current treatment line Is the patient receiving or has he/she received an anti-secretory drug? □ Yes
□ No □ NK
❏ Diazoxide If yes,
❏ Proton pump inhibitor
❏ Other, please state:
□ NK
Treatment line at the enrolment visit: (maximum 4th line)
❏ Treatment started on the day of the enrolment visit as - line ❏ Treatment started before enrolment visit as → Iine
❏ French NET network MDTM
❏ Other MDTM
Treatment decision made in:
□ NK
2.3.2. Characteristics of the pancreatic neuroendocrine tumour on starting the current treatment line or treatment line initiated at enrolment Metastases present on starting the treatment line ongoing or initiated at enrolment?  
□ Yes If yes, Localisation of metastases ( tick more than one if applicable ):  
Lungs  
Bones
□ Yes □ No □ Not known Liver  
lf yes, % of liver invaded:
Peritoneum
□ Not known Other  □ Yes:
□ No final version of 17/07/2018 2.3.3. Comorbidities and history on starting the current treatment line or treatment line initiated at enrolment Lung disease (COPD, Asthma etc.)   □ Yes     □ No If yes, on treatment for lung disease?  
□ Yes    □ No Heart failure
□ Yes
□ No if yes, on treatment for heart failure?  
Left Ventricular Ejection Fraction (LVEF) if available: Coronary heart disease
□ Yes
□ No
□ Yes if yes, on treatment for coronary heart disease?  
□ No Cerebrovascular accident
□ Yes
□ No if yes, on treatment for CVA?  
□ Yes    □ No Hypertension
□ Yes
□ No if yes, on treatment for HT?  
□ Yes    □ No Hypercholesterolaemia
□ Yes
□ No if yes, on treatment for hypercholesterolaemia?  
Diabetes
🙂 Yes
□ No on treatment for type I diabetes?   □ Yes
□ No Type of diabetes:
If yes,
□ Type I
on treatment for type II diabetes?  □ Yes
□ No
□ Type II
Insulin If yes,
□ Yes   □ No Oral anti-diabetics
□ No Renal function Clearance (ml/min): □ < 30
□ [30; 60]
□ >60 Other
□ Yes, please state_
□ No Symptoms of functioning pNET present on starting the current treatment line or treatment line initiated at enrolment?  
□ Yes    □ No Related to:
❏ Gastrinoma
❏ Insulinoma ❏ Glucagonoma
□ VIPoma
❏ Other, please state:
2.3.4 ECOG performance status at enrolment:  
□ 0 2.4 History of the illness Initial diagnosis of pancreatic neuroendocrine tumour 1/
Date of diagnosis:
Tumour at diagnosis:
□ Localised tumour
□ Metastatic tumour Previous local and/or regional cancer treatments During the course of the disease, has the patient received local and/or regional treatments?  
❏ Yes
□ NK
❏ Surgery to primary cancer If yes,
❏ Surgery to liver metastases
❏ Radiofrequency ablation ❏ Chemoembolization/embolization
❏ Other, please state:
Most recent examinations Octreoscan
□ Yes If yes,  Octreoscan, Date:
Octreoscan, Uptake:
□ Yes    □ No    □ NK  
PET scan If yes,  PET scan, Date:
PET scan, Uptake:   □ Yes    □ No    □ NK
Histology Observational study protocol final version of 17/07/2018 Ki67 Value obtained
□ Yes
□ No if yes, Ki67 value:
% or  □  NK
Mitotic index Value obtained
□ No
❏ Yes if yes, mitotic index value: ___
mitoses/field or  □ NK
French NET pathology network 2nd opinion
□ Not known History of previous tumour-directed systemic treatments Please describe all previous treatment lines:  
| Table 1 - Previous tumour-directed cancer treatments                                                                                 | Reason for stopping    |                    |                     |                  |
|--------------------------------------------------------------------------------------------------------------------------------------|------------------------|--------------------|---------------------|------------------|
| Name                                                                                                                                 | Treatment line         | Combined with      | Duration            |                  |
| somatostatin                                                                                                                         |                        |                    |                     |                  |
| analogues                                                                                                                            |                        |                    |                     |                  |
| Chemotherapy:                                                                                                                        | ❏ First line           | ❏ Yes              | (eCRF               | ❏ Adverse event' |
| ❏ Octreotide                                                                                                                         | display:               |                    |                     |                  |
| 口 5 FU                                                                                                                              | ❏ Second line          | ❏ Progression      |                     |                  |
| ❏ Lanreotide                                                                                                                         | Duration               |                    |                     |                  |
| ❏ Capecitabine (Xeloda®)                                                                                                             | ❏ Third line           | D                  | Scheduled treatment |                  |
| recorded                                                                                                                             |                        |                    |                     |                  |
| ❏ Doxorubicin (Adriamycin®)                                                                                                          | discontinuation        |                    |                     |                  |
| oly if the                                                                                                                           |                        |                    |                     |                  |
| ❏ Streptozocin (Zanosar®)                                                                                                            | treatment is           | ❏ Patient decision |                     |                  |
| a TT)                                                                                                                                |                        |                    |                     |                  |
| ❏ Temolozomide (Temodal®)                                                                                                            |                        |                    |                     |                  |
| ❏ Dacarbazine (Deticene®)                                                                                                            |                        |                    |                     |                  |
| ❏ Oxaliplatin (Eloxatin®)                                                                                                            | ❏ Other, please state: |                    |                     |                  |
| months                                                                                                                               |                        |                    |                     |                  |
| ❏ Gemcitabine (Gemzar®)                                                                                                              |                        |                    |                     |                  |
| ❏ Cisplatin                                                                                                                          | □ NK                   |                    |                     |                  |
| ❏ VP-16                                                                                                                              | please                 | state:             |                     |                  |
| o                                                                                                                                    | Other,                 |                    |                     |                  |
| ❏ Interferon Alpha                                                                                                                   |                        |                    |                     |                  |
| Targeted therapies                                                                                                                   |                        |                    |                     |                  |
| ❏ Everolimus                                                                                                                         |                        |                    |                     |                  |
| ❏ Sunitinib                                                                                                                          |                        |                    |                     |                  |
| Somatostatin analogues                                                                                                               |                        |                    |                     |                  |
| ❏ Octreotide                                                                                                                         |                        |                    |                     |                  |
| ❏ Lanreotide                                                                                                                         |                        |                    |                     |                  |
| ❏ Radionuclide therapy                                                                                                               |                        |                    |                     |                  |
| D                                                                                                                                    | Other,                 | please             | state:              |                  |
| * In the event of an AE related to a Pfizer product, please complete the safety section of the CRF (lines may be added if there have |                        |                    |                     |                  |
| been more treatments, up to a limit of 3 previous lines)                                                                             |                        |                    |                     |                  |  
been more treatments, up to a limit of 3 previous lines)
final version of 17/07/2018 2.5 Treatment line ongoing at the enrolment visit Depending on the treatment ticked in 2.3 the corresponding screen will be displayed SUNITINIB screen - Treatment initiation EVEROLIMUS screen - Treatment initiation CHEMOTHERAPY screen - Treatment initiation INTERFERON ALPHA screen - Treatment initiation SOMATOSTATIN ANALOGUE screen - Treatment initiation RADIONUCLIDE THERAPY screen - Treatment initiation Treatment initiation SUNITINIB screen For all cases of treatment with sunitinib initiated on the day of enrolment or before the enrolment visit (treatment line ongoing)
Treatment with sunitinib initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:  □ Octreotide
□ Lanreotide
□ Other, please state:
1)
2)
Date of d1 of cycle 1:
Dose and dosage regimen:
□ 37.5 mg/day
□ 25 mg/day □ Other, please state: ـ
For all cases of treatment with sunitinib initiated before the enrolment visit (treatment line ongoing)
Has there been a stepwise change in dose since treatment was started?  
□ Yes
□ No If yes, please describe the stepwise changes in dose:  
| Table 2a - Stepwise dose changes (sunitinib)         |                        |                   |                      |
|------------------------------------------------------|------------------------|-------------------|----------------------|
| Date                                                 | New dose step (mg/day) | Reason for change |                      |
| __                                                   | □ 25                   | □ 37.5            | ❏ Adverse event'     |
| (DD/MM/YYYY)                                         | □ 50                   | □ 62.5            | □ Patient's decision |
| □ Other: للا للا                                     | □ Doctor's decision    |                   |                      |
| □ Other, please state:                               |                        |                   |                      |
| (Lines may be added if there have been more changes) |                        |                   |                      |  
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
Has treatment with sunitinib been interrupted (interruption > 7 consecutive days) between treatment initiation and enrolment in the study?  
If yes, please describe each interruption:  
| Table 3a - Temporary treatment interruptions (sunitinib)                                           |                      |                  |                 |                                 |
|----------------------------------------------------------------------------------------------------|----------------------|------------------|-----------------|---------------------------------|
| Start                                                                                              | date                 | of               | Duration (days) | If yes, reason for interruption |
| interruption                                                                                       |                      |                  |                 |                                 |
| __                                                                                                 |                      | ❏ Adverse event* |                 |                                 |
| (DD/MM/YYYY)                                                                                       | ❏ Patient's decision |                  |                 |                                 |
| □ Doctor's decision                                                                                |                      |                  |                 |                                 |
| □ Other, please state:                                                                             |                      |                  |                 |                                 |
| (Lines may be added if there have been more interruptions)                                         |                      |                  |                 |                                 |
| * In the event of an AE related to a Pfizer product, please complete the safety section of the CRF |                      |                  |                 |                                 |  
final version of 17/07/2018 EVEROLIMUS screen   -   Treatment initiation For all cases of treatment with everolimus initiated on the day of enrolment or before the enrolment visit (treatment line ongoing)
Treatment with everolimus initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:  □ Octreotide
□ Lanreotide
□ Other treatment, please state:
1) 2)
Date of initiation:
□ 5 mg/day Dose and dosage regimen:
□ 10 mg/day
□ Other, please state: ـ
For all cases of treatment with everolimus initiated before the enrolment visit (treatment line ongoing)
Has there been a stepwise change in dose since treatment was started?  
□ No If yes, please describe the stepwise changes in dose:  
| Table 2b - Stepwise dose changes (everolimus)        |                               |                           |
|------------------------------------------------------|-------------------------------|---------------------------|
| Date                                                 | New dose step (mg/day)        | Reason for change         |
| __                                                   | □ 5                           | □ Adverse event           |
| (DD/MM/YYYY)                                         | □ 10                          | □ Related to everolimus * |
| 口 Other لال                                         | □ Not related to everolimus** |                           |
| ❏ Patient's decision                                 |                               |                           |
| □ Doctor's decision                                  |                               |                           |
| □ Other, please state;                               |                               |                           |
| (Lines may be added if there have been more changes) |                               |                           |  
(Lines may be added if there have been more changes)
* In the event of an AE related to a everolimus, please complete the safety section of the CRF
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
Has treatment with everolimus been interrupted (interruption > 7 consecutive days) between treatment initiation and enrolment in the study?  
□ Yes
□ No If yes, please describe each interruption:  
|  Table 3b - Temporary treatment interruptions (everolimus)   |                           |                                 |
|--------------------------------------------------------------|---------------------------|---------------------------------|
| Start date of interruption                                   | Duration                  | If yes, reason for interruption |
| (days)                                                       |                           |                                 |
| __                                                           | IIII                      | □ Adverse event                 |
| (DD/MM/YYYY)                                                 | □ Related to everolimus * |                                 |
| □ Not related to everolimus**                                |                           |                                 |
| □ Patient's decision                                         |                           |                                 |
| □ Doctor's decision                                          |                           |                                 |
| □ Other, please state:                                       |                           |                                 |
| (Lines may be added if there have been more interruptions)   |                           |                                 |  
* In the event of an AE related to a everolimus, please complete the safety section of the CRF
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
Observational study protocol final version of 17/07/2018 CHEMOTHERAPY screen - Treatment initiation For all cases of treatment with chemotherapy initiated on the day of enrolment or before the enrolment visit
(treatment line ongoing) Treatment: [Pre-completed with the treatment entered in 2.3.1]
Treatment initiated as:
□ Chemotherapy only □ Combination therapy with:
□ A somatostatin analogue Please state:  □ Octreotide
□ Lanreotide
□ Other treatment, please state:
Date of initiation of the first treatment: ⌒ J / ⌒ J / ⌒ J / ⌒ ⌒ J / ⌒ ⌒ ⌒ (DD/MM/YYY)
Number of cycles delivered:
Cycle schedule: ☐ 7 days For all cases of treatment with chemotherapy initiated before the enrolment visit (treatment line ongoing)
Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:  
| Has there been a stepwise change in dose since treatment was started?   □ Yes □ No                 |                        |                      |
|----------------------------------------------------------------------------------------------------|------------------------|----------------------|
| If yes, please describe the stepwise changes in dose:                                              |                        |                      |
| Table 2c - Stepwise dose changes (chemotherapy)                                                    |                        |                      |
| Date                                                                                               | Dose change            | Reason for change    |
| [[                                                                                                 | ❏ Adverse event*       |                      |
| (DD/MM/YYYY)                                                                                       | ❏ Increase             | ❏ Patient's decision |
| □ Doctor's decision                                                                                |                        |                      |
| □ Decrease                                                                                         | □ Other, please state: |                      |
| (Lines may be added if there have been more changes)                                               |                        |                      |
| * In the event of an AE related to a Pfizer product, please complete the safety section of the CRF |                        |                      |  
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment between initiation and enrolment in the study?   □ Yes
□ No If yes, reason for postponing:
❏ Adverse event*
❏ Patient's decision □ Doctor's decision
□ Other, please state:
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
final version of 17/07/2018 INTERFERON ALPHA screen - Treatment initiation For all cases of treatment with interferon alpha initiated on the day of enrolment or before the enrolment visit
(treatment line ongoing) Treatment with interferon initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:  □ Octreotide
□ Lanreotide
□ Other, please state:
1)
2)
Type of treatment:
□ Pegylated Date of initiation: لــلــلــلــ / لــلــلــلــ (DD/MM/YYY)
Initial dose: لالالا MIU/day For all cases of treatment with interferon alpha initiated before the enrolment visit (treatment line ongoing)
Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:  
| Table 2d - Stepwise dose changes (IFN-a)                                                           |                      |
|----------------------------------------------------------------------------------------------------|----------------------|
| Reason for change                                                                                  |                      |
| Date                                                                                               |                      |
| -----                                                                                              | ❏ Adverse event*     |
| (DD/MM/YYYY)                                                                                       | ❏ Patient's decision |
| □ Doctor's decision                                                                                |                      |
| □ Other, please state:                                                                             |                      |
| (Lines may be added if there have been more changes)                                               |                      |
| * In the event of an AE related to a Pfizer product, please complete the safety section of the CRF |                      |  
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
Has treatment with IFN-α been postponed by more than 7 consecutive days from the scheduled date of treatment between initiation and enrolment in the study?   □ Yes
□ No If yes, reason for postponing:
□ Adverse event
□ Patient's decision
□ Doctor's decision
□ Other, please state:
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
final version of 17/07/2018 SOMATOSTATIN ANALOGUE screen - Treatment initiation For all cases of treatment with somatostatin analogues initiated on the day of enrolment or before the enrolment visit (treatment line ongoing)
Treatment with somatostatin analogues as:
□ Monotherapy
□ Combination therapy, please state: 1)
2)
Treatment: [Pre-completed with the treatment entered in 2.3.1]
Date of initiation: Dose: (Screen displayed depends on the treatment) If Octreotide: □ 10 mg/28days   □ 20 mg/28days   □ 30 mg/28days   □ other, please state: If Lanreotide: □ 60 mg/28days   □ 90 mg/28days   □ 120 mg/28days   □ other, please state:
For all cases of treatment with somatostatin analogues initiated before the enrolment visit Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:
Table 2e - Stepwise dose changes (SA)  
|  Date                                                | Reason for change    |
|------------------------------------------------------|----------------------|
| __                                                   | ❏ Adverse event'     |
| (DD/MM/YYY)                                          | □ Patient's decision |
| □ Doctor's decision                                  |                      |
| □ Other, please state:                               |                      |
| (Lines may be added if there have been more changes) |                      |  
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment between initiation and enrolment in the study?   □ Yes
□ No If yes, reason for postponing:
❏ Adverse event*
❏ Patient's decision □ Doctor's decision □ Other, please state:
* In the event of an AE related to a Pfizer product, please complete the safety section of the CRF  
RADIONUCLIDE THERAPY screen - **Treatment initiation**
For all cases of treatment with radionuclide therapy initiated on the day of enrolment or before the enrolment visit
(treatment line ongoing)
Treatment with radionuclide therapy initiated as:
Monotherapy Combination therapy with:
A somatostatin analogue Please state:  Octreotide Lanreotide Other treatment, please state: 1) ___________
2) ___________
Date of initiation:  /  /  (DD/MM/YYYY)
Place of treatment:  France Netherlands Switzerland Other, please state: __________
Number of treatments administered since initiation:
Radioisotope:  Lutetium Indium Ytrium 2.6 Safety - onset of adverse events (recorded retrospectively)
Safety data are only recorded retrospectively for "prevalent case" patients, which is any patient whose treatment had already been started before enrolment irrespective of the treatment (targeted therapies or other treatments)
A
For all treatment initiated before the enrolment visit:
Has the patient presented with serious or non-serious adverse events related to a Pfizer product since the first treatment line for this disease? ❏ Yes
□ No lf yes, please state:
Please complete the adverse events table below for all serious or non-serious adverse events related to a Pfizer product reported by the patient since the first treatment line for this disease A
For all cases of treatment with everolimus initiated before the enrolment visit (treatment line ongoing):
Has the patient presented with serious or non-serious adverse events related to everolimus since initiation of the current treatment line? ❏ Yes  ❏ No lf yes, please state:
Please complete the adverse events table below for all serious or non-serious adverse events related to everolimus reported by the patient since initiation of the current treatment line
final version of 17/07/2018
description of the adverse event

| Description of the adverse event:                  |                   |                     |                   |             |                |           |
|----------------------------------------------------|-------------------|---------------------|-------------------|-------------|----------------|-----------|
| Table 4 - Safety                                   | CTCAE             |                     |                   |             |                |           |
| Description of Date of Outcome                     | Severity          | Seriousn  Causality | Action concerning |             |                |           |
| the event                                          | onset             | grade               | ess               | the         | suspected      |           |
| treatment                                          |                   |                     |                   |             |                |           |
| -/-/---                                            |                   | ■Mild               | - Grade 1         |             | (re-ticked not | ❏ Stopped |
| If resolved,                                       | ■Moderate         | ♦ Grade 2           | Not               | changeable) | temporarily    |           |
| Date of resolution:                                | ■Severe           |                     | serious           | ❏ Stopped   |                |           |
|                                                    |                   |                     |                   |             |                |           |
| -/-/-                                              |                   | definitively        |                   |             |                |           |
| ❏ Resolved with                                    | ❏ Grade 5         | 🙂 Dosage increase  |                   |             |                |           |
| □ Everolimus                                       |                   |                     |                   |             |                |           |
| sequelae                                           | ❏ Dosage decrease |                     |                   |             |                |           |
| If resolved,                                       | ❏ Continue        |                     |                   |             |                |           |
| Date of resolution:                                | unchanged         |                     |                   |             |                |           |
| -/-/-                                              | ❏ Unknown         |                     |                   |             |                |           |
| Resolution                                         |                   |                     |                   |             |                |           |
| ongoing                                            |                   |                     |                   |             |                |           |
| ❏ Not resolved                                     |                   |                     |                   |             |                |           |
| ❏ Unknown                                          |                   |                     |                   |             |                |           |
| (Lines may be added if more AE have been reported) |                   |                     |                   |             |                |           |
final version of 17/07/2018
tumour assessment visit

At each follow-up visit, to take place approximately every 2 - 3 months in line with the site's usual practices for tumour assessment, the following data will be recorded:
Date of the tumour assessment visit: لولو / لولو / لولو / لولو (DD/MM/YYY) or □ Not done At the end of study visit, to take place approximately 2 years after enrolment:
The patient has been monitored for 2 years: ❏ Last follow-up visit (scheduled end of study)
3.1 Tumour assessment Examination date:
lmaging examination performed for tumour assessment (tick all that apply):
□ CT scan
□ Ultrasound Radiological response to treatment in the investigator's opinion (based on RECIST criteria)
□ CR (Complete response) □ PR (Partial response)
□ SD (Stable disease)
□ PD (Progressive disease) Date of progression:
□ NE (Not Evaluable)
Reason:
Clinical response in investigator's opinion: □ Yes
□ No Date of progression:
❏ Progressive disease
□ Stable disease
□ Response 3.2 Clinical parameters ECOG performance status Value obtained:
□ No
□ 2
□ 3
□ 4
❏ Unknown If yes,     Value: □ 0
□ 1 final version of 17/07/2018 3.3 Therapeutic management since last tumour assessment Since the last documented visit, the cancer treatment may have been continued or may have changed on one or more occasions. The participating doctor must enter all of the cancer treatment lines prescribed to the patient, and then complete the corresponding screens.  
Therapeutic management since the last documented tumour assessment visit on [date of the last documented visit] and up to and including today's visit:
If a treatment was "ongoing" at the end of the previous visit (will be checked by the eCRF):
❏ Treatment with [name of treatment] that was ongoing at the previous visit continued lf treatment continued:
ls [combined treatment entered] being continued?  
❏ Yes    □ No If no, reason for stopping [combined treatment entered]:
□ Patient's decision
□ Doctor's decision
□ Other, please state: __
□ No  
Have any new combined treatments been started since the last visit?  
□ A somatostatin analogue If yes, which ones?  
□ Octreotide Please state:
□ Lanreotide
□ Other treatment, please state:
1)
2)
❏ Treatment with (name of treatment) that was ongoing at previous visit stopped definitively Date stopped definitively (see Table 5)
If stopped, Reason for stopping treatment (see Table 5)
Was [combined treatment entered] still ongoing on the date when [name of the treatment line stopped] was stopped?  □ Yes  □ No If no, Reason for stopping [combined treatment entered]:  □ Adverse event*
❏ Patient's decision
□ Doctor's decision
□ Other, please state: _
Have any new combined treatments been started between the last visit and the date of stopping [name of the treatment line stopped]: □ Yes  □ No lf yes, which ones?:
□ A somatostatin analogue Please state:
□ Lanreotide
□ Other treatment, please state:   1)
Has a new treatment line been put in place?        Yes If yes, please describe all new lines of cancer treatment put in place since the last tumour assessment visit, including the treatment in place at the end of today's visit (see Table 5).  
If No, if a period of treatment abstention is extended, the patient continues to be followed for 2 years as planned (unless deceased or lost to follow-up).  
If no treatment was "ongoing" at the end of the previous visit (will be checked by the eCRF):
❏ Treatment abstention extended (apart from temporary treatment interruptions)
If Extended, if a period of treatment abstention is extended, the patient continues to be followed for 2 years as planned (unless deceased or lost to follow-up).  
❏ New treatment line resumed If Resumed, please describe all new lines of cancer treatment put in place since the last tumour assessment visit, including the treatment in place at the end of today's visit (see Table 5).  
| Observational study protocol                                                                                         | final version of 17/07/2018   |                            |                       |                    |      |
|----------------------------------------------------------------------------------------------------------------------|-------------------------------|----------------------------|-----------------------|--------------------|------|
| Table 5 - Therapeutic management                                                                                     |                               |                            |                       |                    |      |
| Treatment                                                                                                            | Start date                    | Date                       | stopped               | lf stopped, reason |      |
| definitively                                                                                                         | If stopped, Reason            |                            |                       |                    |      |
| Treatment ongoing at previous visit                                                                                  | Start                         | date                       | h                     | stopped,           | date |
| (auto)                                                                                                               | (auto)                        | stopped                    | ❏ Disease progression |                    |      |
| ❏ AE                                                                                                                 |                               |                            |                       |                    |      |
| If AE, has an AE reporting                                                                                           |                               |                            |                       |                    |      |
| If not, Ongoing.                                                                                                     | form been completed?:         |                            |                       |                    |      |
| ❏ Yes ❏ No                                                                                                           |                               |                            |                       |                    |      |
| lf no, please report the AE*                                                                                         |                               |                            |                       |                    |      |
| ❏ Patient's decision                                                                                                 |                               |                            |                       |                    |      |
| ❏ Doctor's decision, if so                                                                                           |                               |                            |                       |                    |      |
| please state why:                                                                                                    |                               |                            |                       |                    |      |
| ❏ Cumulative dose reached                                                                                            |                               |                            |                       |                    |      |
| ❏ Scheduled stop                                                                                                     |                               |                            |                       |                    |      |
| ❏ Optimum response                                                                                                   |                               |                            |                       |                    |      |
| D                                                                                                                    | Other,                        | please                     | state:                |                    |      |
| ❏ Lost to follow-up                                                                                                  |                               |                            |                       |                    |      |
| ❏ Death → redirects to the                                                                                           |                               |                            |                       |                    |      |
| Anticipated end                                                                                                      | of                            | study                      |                       |                    |      |
| questionnaire                                                                                                        |                               |                            |                       |                    |      |
| Targeted therapy                                                                                                     | y                             | stopped,                   | date                  | If stopped, Reason |      |
| ❏ everolimus                                                                                                         | stopped                       | ❏ Disease progression      |                       |                    |      |
| ❏ sunitinib                                                                                                          | D AE                          |                            |                       |                    |      |
| Chemotherapy                                                                                                         | - If not, Ongoing.            | If AE, has an AE reporting |                       |                    |      |
|                                                                                                                      | form been completed?          |                            |                       |                    |      |
| ❏ Capecitabine (Xeloda®)                                                                                             | ❏ Yes ❏ No                    |                            |                       |                    |      |
| ❏ Doxorubicin (Adriamycin®)                                                                                          | If no, please report the AE*  |                            |                       |                    |      |
| ❏ Streptozocin (Zanosar®)                                                                                            | ❏ Patient's decision          |                            |                       |                    |      |
| ❏ Temolozomide (Temodal®)                                                                                            | ❏ Doctor's decision, if so    |                            |                       |                    |      |
| ❏ Dacarbazine (Deticene®)                                                                                            | please state why:             |                            |                       |                    |      |
| ❏ Oxaliplatin (Eloxatin®)                                                                                            | ❏ Cumulative dose reached     |                            |                       |                    |      |
| ❏ Gemcitabine (Gemzar®)                                                                                              | ❏ Scheduled stop              |                            |                       |                    |      |
| ❏ Cisplatin                                                                                                          | ❏ Optimum response            |                            |                       |                    |      |
|                                                                                                                      | o                             | Other,                     | please                | state:             |      |
| ❏ Other, please state:                                                                                               | ❏ Lost to follow-up           |                            |                       |                    |      |
| Somatostatin analogues                                                                                               |                               |                            |                       |                    |      |
| ❏ Octreotide                                                                                                         | ❏ Death → redirects to the    |                            |                       |                    |      |
| ❏ Lanreotide                                                                                                         | Anticipated end               | of                         | study                 |                    |      |
| Interferon alpha                                                                                                     | questionnaire                 |                            |                       |                    |      |
| ❏ Interferon alpha                                                                                                   |                               |                            |                       |                    |      |
| Radionuclide therapy                                                                                                 |                               |                            |                       |                    |      |
| ❏ Radionuclide therapy                                                                                               |                               |                            |                       |                    |      |
| Other                                                                                                                |                               |                            |                       |                    |      |
| ❏ Other, please state:                                                                                               |                               |                            |                       |                    |      |
| (lines may be added if there are more treatments to enter)                                                           |                               |                            |                       |                    |      |
| * If there has been an adverse event, please complete the safety section of the CRF within the stated timeframe      |                               |                            |                       |                    |      |
| If no "ongoing" treatment is entered and if the patient is not deceased or lost to follow-up (will be checked by the |                               |                            |                       |                    |      |  
eCRF):
Is the patient receiving a new treatment line targeting the tumour at the end of today's visit?   □ Yes
□ No If yes, please describe the new treatment line targeting the tumour that was put in place at today's visit (see Table 5)
If not, the following is displayed:
The patient follow-up phase in the study is set at 2 years. Please repeat the follow-up visit at the next tumour assessment visit.  
For each line of cancer treatment entered, the participating doctor will be redirected to the corresponding screen.  
If the treatment has been continued since the last documented visit SUNITINIB screen - Treatment continued EVEROLIMUS screen - Treatment continued CHEMOTHERAPY screen - Treatment continued INTERFERON ALPHA screen - Treatment continued SOMATOSTATIN ANALOGUE screen - Treatment continued RADIONUCLIDE THERAPY screen - Treatment continued If the treatment has been started since the last documented visit SUNITINIB screen - New treatment line EVEROLIMUS screen - New treatment line CHEMOTHERAPY screen - New treatment line INTERFERON ALPHA screen - New treatment line SOMATOSTATIN ANALOGUE screen - New treatment line RADIONUCLIDE THERAPY screen - New treatment line final version of 17/07/2018
final version of 17/07/2018
sunitinib screen - treatment continued

If treated with sunitinib:
Has there been a stepwise dose change since the last tumour assessment visit on [date of last tumour assessment visit entered]?  
□ No If yes, please describe the stepwise changes in dose:  
| Table 2a - Stepwise dose changes (sunitinib)         |                                |
|------------------------------------------------------|--------------------------------|
| Date                                                 | If yes, new dose step (mg/day) |
| □ 25                                                 | □ 37.5                         |
| /                                                    | □ 50                           |
| (DD/MM/YYYY)                                         | □ Other: لال                   |
| (Lines may be added if there have been more changes) |                                |  
| Reason for change      |
|------------------------|
| ❏ Adverse event*       |
| □ Patient's decision   |
| □ Doctor's decision    |
| □ Other, please state; |  
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with sunitinib been interrupted temporarily (interruption > 7 consecutive days) since the last tumour assessment visit on [date of last tumour assessment visit entered]?  
🙂 Yes
□ No If yes, please describe each interruption:
Table 3a - Temporary treatment interruptions (sunitinib)
If yes, reason for interruption Duration (days)
Start date of interruption  
  
/
(DD/MM/YYYY)  
| □□                     | ❏ Adverse event*   |
|------------------------|--------------------|
| □ Patient's decision   |                    |
| □ Doctor's decision    |                    |
| □ Other, please state: |                    |  
(Lines may be added if there have been more interruptions)
* In the event of an adverse event, please complete the safety section of the CRF
SUNITINIB screen  -   New treatment line For all cases of treatment with sunitinib initiated since the last documented visit Treatment with sunitinib initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:   □ Octreotide
□ Lanreotide
□ Other treatment, please state: 1)
2)
Date of d1 of cycle 1: مالم / مالم / مالم (DD/MM/YYY)
Dose and dosage regimen:
□ 37.5 mg/day
□ 25 mg/day
❏ Other, please state:
Has there been a stepwise change in dose since treatment was started?  
If yes, please describe the stepwise changes in dose:
Table 2a - Stepwise dose changes (sunitinib)
□ Yes
□ No Date
__
I  
|  New dose step (mg/day)   | Reason for change      |                      |
|---------------------------|------------------------|----------------------|
| □ 25                      | □ 37.5                 | ❏ Adverse event*     |
| □ 50                      |                        | ❏ Patient's decision |
| □ Doctor's decision       |                        |                      |
| ❏ Other:                  | □ Other, please state: |                      |  
(DD/MM/YYY)
(Lines may be added if there have been more changes)
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with sunitinib been interrupted (interruption > 7 consecutive days) since treatment initiation?  
□ Yes If yes, please describe each interruption:
Observational study protocol final version of 17/07/2018  
| Table 3a - Temporary treatment interruptions (sunitinib)   |                      |                       |                                 |
|------------------------------------------------------------|----------------------|-----------------------|---------------------------------|
| Start                                                      | date                 | of    Duration (days) | lf yes, reason for interruption |
| interruption                                               | __                   | □ Adverse event*      |                                 |
| AAA                                                        | /                    |                       |                                 |
| J J J                                                      | □ Patient's decision |                       |                                 |
| (DD/MM/YYYY)                                               | □ Doctor's decision  |                       |                                 |
| □ Other, please state:                                     |                      |                       |                                 |
| (Lines may be added if there have been more interruptions) |                      |                       |                                 |  
* In the event of an adverse event, please complete the safety section of the CRF
final version of 17/07/2018
everolimus screen - treatment continued

If treated with everolimus: Has there been a stepwise dose change since the last tumour assessment visit on (date of last tumour assessment visit entered]?   □ Yes □ No If yes, please describe the stepwise changes in dose:  
| Table 2b - Stepwise dose changes (everolimus)   |                                |                      |
|-------------------------------------------------|--------------------------------|----------------------|
| Date                                            | If yes, new dose step (mg/day) | Reason for change    |
| n                                               | □ 5                            | □ Adverse event'     |
| __                                              |                                |                      |
| I                                               | □ 10                           | ❏ Patient's decision |
| (DD/MM/YYYY)                                    | □ Other الا                    | □ Doctor's decision  |
| □ Other, please state:                          |                                |                      |  
(Lines may be added if there have been more changes) * In the event of an adverse event, please complete the safety section of the CRF
Has treatment with everolimus been interrupted temporarily (interruption > 7 consecutive days) since the last tumour assessment visit on [date of last tumour assessment visit entered]?    □ Yes  
If yes, please describe each interruption:  
| Table 3b - Temporary treatment interruptions (everolimus)   |                      |                       |                                 |
|-------------------------------------------------------------|----------------------|-----------------------|---------------------------------|
| Start                                                       | date                 | of    Duration (days) | If yes, reason for interruption |
| interruption                                                |                      |                       |                                 |
|                                                             | __                   | __                    | □ Adverse event*                |
| 11.1.                                                       | ❏ Patient's decision |                       |                                 |
| (DD/MM/YYYY)                                                | □ Doctor's decision  |                       |                                 |
| □ Other, please state;                                      |                      |                       |                                 |
| (Lines may be added if there have been more interruptions)  |                      |                       |                                 |  
* In the event of an adverse event, please complete the safety section of the CRF
Observational study protocol final version of 17/07/2018 EVEROLIMUS screen   -   New treatment line For all cases of treatment with everolimus initiated since the last documented visit Treatment with everolimus initiated as:
□ Monotherapy □ Combination therapy with:
□ A somatostatin analogue Please state:   □ Octreotide
□ Lanreotide
□ Other treatment, please state:
1)
2)
Date of initiation:
Dose and dosage regimen:
□ 5 mg/day
□ 10 mg/day
□ Other, please state: ـ
Has there been a stepwise change in dose since treatment was started?    □ Yes If yes, please describe the stepwise changes in dose:
Table 2b - Stepwise dose changes (everolimus)
□ No Date New dose step (mg/day)  
AAA  
  
(DD/MM/YYY)
□ 5  
  
  
□ 10  
|  Reason for change     |
|------------------------|
| ❏ Adverse event*       |
| ❏ Patient's decision   |
| □ Doctor's decision    |
| □ Other, please state: |  
□ Other للا  
  
(Lines may be added if there have been more changes)
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with everolimus been interrupted (interruption > 7 consecutive days) since treatment initiation?  
□ Yes   □ No If yes, please describe each interruption:
Table 3b - Temporary treatment interruptions (everolimus)
Duration (days)
Start date  
  
  
of lf yes, reason for interruption interruption 1  
  
__  
  
(DD/MM/YYYY)  
| 1111                   | ❏ Adverse event*   |
|------------------------|--------------------|
| □ Patient's decision   |                    |
| □ Doctor's decision    |                    |
| □ Other, please state: |                    |  
(Lines may be added if there have been more interruptions)
* In the event of an adverse event, please complete the safety section of the CRF
final version of 17/07/2018
chemotherapy screen - treatment continued

If treatment with chemotherapy has been initiated and continued as a combination treatment since last visit: Has there been a stepwise dose change since the last tumour assessment visit on [date of last tumour assessment visit entered]?   □ Yes □ No If yes, please describe the stepwise changes in dose:  
| Table 2c - Stepwise dose changes (chemotherapy)      |             |                      |
|------------------------------------------------------|-------------|----------------------|
| Date                                                 | Dose change | Reason for change    |
| __                                                   | ❏ Increase  | ❏ Adverse event*     |
| (DD/MM/YYY)                                          | □ Decrease  | ❏ Patient's decision |
| ❏ Doctor's decision                                  |             |                      |
| □ Other, please state:                               |             |                      |
| (Lines may be added if there have been more changes) |             |                      |  
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment since the last tumour assessment visit on [date of the last tumour assessment visit entered]?  
Observational study protocol final version of 17/07/2018
□ Yes   □ No If yes, reason for postponing:
❏ Adverse event*
❏ Patient's decision
□ Doctor's decision □ Other, please state:
* In the event of an adverse event, please complete the safety section of the CRF
CHEMOTHERAPY screen   -   New treatment line For all cases of treatment with chemotherapy initiated since the last documented visit Treatment of: [Pre-completed with the treatment entered in 3.3]
Treatment initiated as:
□ Chemotherapy only
□ Combination therapy with:
□ A somatostatin analogue Please state:   □ Octreotide
□ Lanreotide
□ Other treatment, please state:  1)
Date of initiation of the first treatment: ⌒ J / ⌒ J / ⌒ J / ⌒ ⌒ J / ⌒ ⌒ ⌒ (DD/MM/YYY)
Number of cycles delivered:
Cycle schedule: ☐ 7 days Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:  
| Table 2c - Stepwise dose changes (chemotherapy)      |                  |                      |
|------------------------------------------------------|------------------|----------------------|
| Date                                                 | Dose change      | Reason for change    |
| l lange of the seat of the sea                       | □ Adverse event* |                      |
| -                                                    | □ Increase       | □ Patient's decision |
| (DD/MM/YYYY)                                         | □ Decrease       | □ Doctor's decision  |
| □ Other, please state:                               |                  |                      |
| (Lines may be added if there have been more changes) |                  |                      |  
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment since initiation?   □ Yes  □ No If yes, reason for postponing:
❏ Adverse event*
□ Patient's decision □ Doctor's decision
□ Other, please state:
* In the event of an adverse event, please complete the safety section of the CRF
Observational study protocol final version of 17/07/2018
final version of 17/07/2018
interferon alpha screen - treatment

If treated with interferon alpha:
If treatment with Interferon alpha has been initiated and continued as a combination treatment since last visit: Has there been a stepwise dose change since the last tumour assessment visit on ſdate of last tumour assessment visit entered]?  
□ No If yes, please describe the stepwise changes in dose:
Table 2d - Stepwise dose changes (IFN-a)  
| Table 2d - Stepwise dose changes (IFN-a)             |                     |
|------------------------------------------------------|---------------------|
| Date                                                 | Reason for change   |
| ❏ Adverse event*                                     |                     |
| ❏ Patient's decision                                 |                     |
| (DD/MM/YYY)                                          | □ Doctor's decision |
| □ Other, please state:                               |                     |
| (Lines may be added if there have been more changes) |                     |  
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with interferon alpha been postponed by more than 7 consecutive days from the scheduled date of treatment since the last tumour assessment visit on [date of the last tumour assessment visit entered]?  
□ Yes   □ No If yes, reason for postponing:
□ Adverse event
□ Patient's decision
□ Doctor's decision
□ Other, please state:
* In the event of an adverse event, please complete the safety section of the CRF
INTERFERON ALPHA screen  -   New treatment line For all cases of treatment with interferon alpha initiated since the last documented visit Treatment with interferon initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:   □ Octreotide
□ Lanreotide
□ Other treatment, please state:
1)
2)
□ Pegylated Type of treatment:
□ Standard Date of initiation:
Initial dose: لــلــلــ MIU/day Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:
Table 2d - Stepwise dose changes (IFN-a)  
| Date                                                 | Reason for change   |
|------------------------------------------------------|---------------------|
| ❏ Adverse event*                                     |                     |
| □ Patient's decision                                 |                     |
| (DD/MM/YYY)                                          | □ Doctor's decision |
| □ Other, please state:                               |                     |
| (Lines may be added if there have been more changes) |                     |  
(Lines may be added if there have been more changes)
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with IFN-α been postponed from more than 7 consecutive days from the scheduled date of treatment since initiation?  
□ No Observational study protocol final version of 17/07/2018 If yes, reason for postponing:
❏ Adverse event*
❏ Patient's decision
□ Doctor's decision
□ Other, please state:
* In the event of an adverse event, please complete the safety section of the CRF
final version of 17/07/2018
somatostatin analogues screen - treatment

If treated with a somatostatin analogue:
If treatment with a somatostatin analogue has been initiated and continued as a combination treatment since last visit:
Has there been a stepwise dose change since the last tumour assessment visit on [date of last tumour assessment visit entered]?   □ Yes □ No If yes, please describe the stepwise changes in dose:
Table 2e - Stepwise dose changes (SA)
Reason for change Date
□ Adverse event' 77777777777
(DD/MM/YYY)
□ Patient's decision □ Doctor's decision □ Other, please state:
(Lines may be added if there have been more changes)
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment since the last tumour assessment visit on ʃdate of the last tumour assessment visit entered]? □ Yes   □ No If yes, reason for postponing:
❏ Adverse event*
❏ Patient's decision
□ Doctor's decision
□ Other, please state:
* In the event of an adverse event, please complete the safety section of the CRF
Observational study protocol final version of 17/07/2018 SOMATOSTATIN ANALOGUES screen    -   New treatment line For all cases of treatment with somatostatin analogues initiated since last documented visit Treatment: [Pre-completed with the treatment entered in 2.3.1]
Date of initiation: لملــلــلــ / لملــلــلــ (DD/MM/YYYY)
Dose: (Screen displayed depends on the treatment)
If Octreotide: □ 10 mg/28days   □ 20 mg/28days   □ 30 mg/28days   □ other, please state:
If Lanreotide: □ 60 mg/28days   □ 90 mg/28days   □ 120 mg/28days   □ other, please state:
Treatment with somatostatin analogues initiated as:
□ Monotherapy
□ Combination therapy, please state: 1)
2)
Has there been a stepwise change in dose since treatment was started?   □ Yes □ No If yes, please describe the stepwise changes in dose:
Table 2e - Stepwise dose changes (SA)
Date Reason for change
❏ Adverse event*
❏ Patient's decision
(DD/MM/YYY)
□ Doctor's decision
□ Other, please state:
(Lines may be added if there have been more changes)
* In the event of an adverse event, please complete the safety section of the CRF
Has treatment with "name of treatment" been postponed by more than 7 consecutive days from the scheduled date of treatment since initiation?   □ Yes  □ No If yes, reason for postponing:
❏ Adverse event* □ Patient's decision
□ Doctor's decision
□ Other, please state:_
* In the event of an adverse event, please complete the safety section of the CRF
final version of 17/07/2018
radionuclide therapy screen - treatment

If treatment with radionuclide therapy has been initiated and continued as a combination treatment since last visit:
Number of cycles administered since the last visit on [date of last tumour assessment visit entered]: للا RADIONUCLIDE THERAPY screen   -   New treatment line Treatment with radionuclide therapy initiated as:
□ Monotherapy
□ Combination therapy with:
□ A somatostatin analogue Please state:   □ Octreotide
□ Lanreotide
□ Other treatment, please state: 1)
2)
Date of initiation:
Place of treatment:  □ France
□ Netherlands
□ Switzerland
□ Other, please state:
final version of 17/07/2018 Number of cycles administered since initiation: لــلــلــ
R Rodiois otope:
□ Lutetium
□ Indium
□ Ytrium 3.4 Safety - onset of adverse events Has the patient experienced adverse events since the last documented visit on [date of last tumour assessment visit entered]? □ Yes
□ No If yes, please describe all adverse events experienced in the Safety section of the eCRF (see 5. Adverse events recording module)
final version of 17/07/2018
4. anticipated end of study

STATUS OF PATIENT
date of last contact:
❏ Alive Main reason for stopping the study
❏ Does not meet the inclusion criteria at enrolment - exclusion
❏ Patient's decision
❏ Transferred to another treatment centre not participating in the study ❏ Other reason, please state:
date of last contact:
❏ Lost to follow-up
❏ Deceased*
- If deceased, please state Date of death Study medication(s) at the time of death
❏ Sunitinib ❏ Everolimus
❏ Octreotide
🙂 Other treatment, please state:
🙂 Chemotherapy
🙂 Interferon alpha
🙂 Somatostatin analogue other than Octreotide
🙂 Radionuclide therapy Cause of death
❏ Disease progression ❏ Adverse event* not related to a study medication
❏ Adverse event* related to a study medication
*Please complete the safety section of the CRF
TREATMENT ONGOING WHEN PATIENT LAST SEEN
If the anticipated end of study form is completed at a time other than a follow-up visit:
Therapeutic management between the last documented tumour assessment visit on [date of the last documented visit] and up to the anticipated end of study date: → Display section 3.3 Therapeutic management since last tumour assessment
→ Display Table 5 and the screens corresponding to each recorded treatment line DISEASE OUTCOME
Page 85 of 90 Best response to treatment when patient last seen Complete response  Stable disease Partial response  Disease progression Date of the last disease assessment:  /  /  (DD/MM/YYYY)
final version of 17/07/2018  
  
  
5. Adverse events recording module (recorded prospectively)  
  
| Description of the adverse event:                    |             |                    |                                             |                 |         |       |           |
|------------------------------------------------------|-------------|--------------------|---------------------------------------------|-----------------|---------|-------|-----------|
| Table 4 - Safety                                     |             |                    |                                             |                 |         |       |           |
| Description of Date of Outcome                       | Severity    | CTCAE              | Seriousn Causality of the Action concerning |                 |         |       |           |
| the event                                            | onset       | grade              | es                                          | study treatment | the     | study |           |
| treatment                                            |             |                    |                                             |                 |         |       |           |
| -- History of previously described adverse events -- |             |                    |                                             |                 |         |       |           |
| -/--/---                                             | 🎁 Resolved | ■Mild              | 🙂 Grade 1                                  | ◄ Serious       |         |       |           |
| If resolved, Date of → Moderate                      | 🙂 Grade 2  | -                  | Not treatment                               | temporarily     |         |       |           |
| resolution: --/--                                    | ■Severe     | 🙂 Grade 3         | serious                                     | □               | Related | to    | ❏ Stopped |
| ❏ Resolved with                                      | 🙂 Grade 4  | treatment          | definitively                                |                 |         |       |           |
| sequelae                                             | 🙂 Grade 5  | If related, please | 🙂 Dosage increase                          |                 |         |       |           |
| If resolved, Date of                                 | state:      | 🙂 Dosage decrease |                                             |                 |         |       |           |
| resolution: --/--/--                                 | □ Related   | to 🙂 Continue     |                                             |                 |         |       |           |
| 🙂 Resolution ongoing                                | Sunitinib   | unchanged          |                                             |                 |         |       |           |
| 🙂 Not resolved                                      | □ Related   | to                 | ❏ Unknown                                   |                 |         |       |           |
| □ Unknown                                            | Everolimus  | ❏ None             |                                             |                 |         |       |           |
| ❏ Other treatment,                                   |             |                    |                                             |                 |         |       |           |
| please state:                                        |             |                    |                                             |                 |         |       |           |
| ❏ Chemotherapy                                       |             |                    |                                             |                 |         |       |           |
| 🙂 Interferon alpha                                  |             |                    |                                             |                 |         |       |           |
| ❏ Somatostatin                                       |             |                    |                                             |                 |         |       |           |
| analogue                                             |             |                    |                                             |                 |         |       |           |
| ❏ Radionuclide                                       |             |                    |                                             |                 |         |       |           |
| therapy                                              |             |                    |                                             |                 |         |       |           |
| (Lines may be added if more AE have been reported)   |             |                    |                                             |                 |         |       |           |  
  
Appendix AE reporting form Non-interventional study adverse events reporting form *For internal usage by Pfizer /Novartis* AE declaration number (*please state if known)* Premises n° Date of declaration 0 0 0 0 0 0 0 0  
  
PROTOCOL/STUDY NUMBER SITE NUMBER PATIENT IDENTITY NUMBER  
| Study title:  Initial declaration                                                                                                                                                                                                                                             | Follow-up declaration                                                                                                                                                                                                                                                                                                    | Country of onset of the event: France Ethnic origin:                                                                                                                              |                                          |                                                             |                  |              |         |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------|-------------------------------------------------------------|------------------|--------------|---------|
| Patient                                                                                                                                                                                                                                                                       | Age                                                                                                                                                                                                                                                                                                                      | Height                                                                                                                                                                            | cm                                       | No requirement to enter in accordance with local regulation |                  |              |         |
| details                                                                                                                                                                                                                                                                       | Male                                                                                                                                                                                                                                                                                                                     | Female                                                                                                                                                                            | Weight                                   | kg                                                          |                  |              |         |
| If                                                                                                                                                                                                                                                                            | patient                                                                                                                                                                                                                                                                                                                  | Date of death                                                                                                                                                                     | Cause(s) of death                        | Determined by autopsy: Y                                    | N                | Unknown      |         |
| deceased:                                                                                                                                                                                                                                                                     | If yes, cause of death determined by autopsy:                                                                                                                                                                                                                                                                            |                                                                                                                                                                                   |                                          |                                                             |                  |              |         |
| Patient medical history                                                                                                                                                                                                                                                       | None                                                                                                                                                                                                                                                                                                                     | State the relevant medical history below. Include other diseases present at the time of the  event and pre-existing conditions. If more space is needed, use copies of this page. |                                          |                                                             |                  |              |         |
| Unknown                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                   |                                          |                                                             |                  |              |         |
| Disease (please state)                                                                                                                                                                                                                                                        | Date                                                                                                                                                                                                                                                                                                                     | of                                                                                                                                                                                | End                                      | Tick here if                                                | Relevant details |              |         |
| onset                                                                                                                                                                                                                                                                         | date                                                                                                                                                                                                                                                                                                                     | ongoing                                                                                                                                                                           | Include surgical interventions and dates |                                                             |                  |              |         |
|                                                                                                                                                                                                                                                                               | Tick                                                                                                                                                                                                                                                                                                                     | if                                                                                                                                                                                | the                                      | Tick here if                                                |                  |              |         |
| medication is by                                                                                                                                                                                                                                                              | Dose                                                                                                                                                                                                                                                                                                                     | Units                                                                                                                                                                             | Frequency                                | Date                                                        | of               | End          | ongoing |
| Pfizer                                                                                                                                                                                                                                                                        | Novarti                                                                                                                                                                                                                                                                                                                  | onset                                                                                                                                                                             | date                                     |                                                             |                  |              |         |
| s                                                                                                                                                                                                                                                                             |                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                   |                                          |                                                             |                  |              |         |
| Study medication (brand name and  generic name) formulation, route of  administration, indication     Treatments received in the 28 days preceding the onset of the AE In the 28 days preceding the onset of the AE, did the patient receive at least one dose of  Sunitinib? | Yes                                                                                                                                                                                                                                                                                                                      | No                                                                                                                                                                                |                                          |                                                             |                  |              |         |
| In the 28 days preceding the onset of the AE, did the patient received at least one dose of a  Pfizer study product (other than Sunitinib)?                                                                                                                                   | Yes                                                                                                                                                                                                                                                                                                                      | No                                                                                                                                                                                |  NK                                     |                                                             |                  |              |         |
| In the 28 days preceding the onset of the AE, did the patient receive at least one dose of  Everolimus?                                                                                                                                                                       | Yes                                                                                                                                                                                                                                                                                                                      | No                                                                                                                                                                                |                                          |                                                             |                  |              |         |
| In the 28 days preceding the onset of the AE, did the patient receive at least one dose of  Octreotide?                                                                                                                                                                       | Yes                                                                                                                                                                                                                                                                                                                      | No                                                                                                                                                                                |                                          |                                                             |                  |              |         |
| Concomitant medications None  Unknown                                                                                                                                                                                                                                         | State below any concomitant medications taken in the two weeks preceding the onset of the event.  Exclude all medications that were only administered over two weeks before the event, and any  medication used to treat the event or taken after onset of the event. If more space is needed, use copies  of this page. |                                                                                                                                                                                   |                                          |                                                             |                  |              |         |
| Name of the medication (brand  and generic names)                                                                                                                                                                                                                             | Reason for use                                                                                                                                                                                                                                                                                                           | Administration route                                                                                                                                                              | Date                                     | of                                                          | End              | Tick here if |         |
| onset                                                                                                                                                                                                                                                                         | date                                                                                                                                                                                                                                                                                                                     | ongoing                                                                                                                                                                           |                                          |                                                             |                  |              |         |
|                                                                                                                                                                                                                                                                               |                                                                                                                                                                                                                                                                                                                          |                                                                                                                                                                                   |                                          |                                                             |                  |              |         |  
| Relevant tests              | State only the results of tests relevant to confirmation of the adverse event(s), for example blood tests or  diagnostic imaging. If more space is needed, use copies of this page.   |                              |       |                   |     |          |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------|-------|-------------------|-----|----------|
| Test                        | Date                                                                                                                                                                                  | Result                       | Units | Normal values Min | Max | Comments |
| Version 5.0_FR, August 2016 | Page ___ of ___                                                                                                                                                                       | Confidential Pfizer/Novartis |       |                   |     |          |  
| Non-interventional study adverse events reporting form                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | For internal usage by Pfizer /Novartis                                                                                                                      |                         |      |       |        |        |          |        |       |      |       |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|------|-------|--------|--------|----------|--------|-------|------|-------|
| AE declaration number (please state if known)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Premises n°                                                                                                                                                 | Date of declaration     |      |       |        |        |          |        |       |      |       |
| 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | 0                                                                                                                                                           | 0                       | 0    | 0     | 0      | 0      | 0        |        |       |      |       |
| PROTOCOL/STUDY NUMBER                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | SITE NUMBER                                                                                                                                                 | PATIENT IDENTITY NUMBER |      |       |        |        |          |        |       |      |       |
| ADVERSE                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      | EVENTS                                                                                                                                                      | (if                     | more | than  | two,   | please | use      | copies | of    | this | page) |
| State                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | the                                                                                                                                                         | diagnosis               | if   | known | rather | than   | symptoms | or     | signs |      |       |
| Designation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | of                                                                                                                                                          | the                     |      |       |        |        |          |        |       |      |       |
| adverse event  Date of  onset:  Was the event serious?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | Yes                                                                                                                                                         | No                      |      |       |        |        |          |        |       |      |       |
| If yes, please state the serious event criteria below:  Serious event criteria (tick all that apply): Death Life threatening  Hospitalisation/prolonged existing hospitalisation Persistent/significant incapacity/disability  Congenital anomaly/birth defect Medically important event Status on the date of  reporting or of death:  Resolution }  Resolution with sequelae }  Resolution ongoing  Not resolved Unknown Is there a reasonable possibility that the event may have been  linked to a study medication? Yes No If yes, please state the study medication:   | Designation                                                                                                                                                 | of                      | the  |       |        |        |          |        |       |      |       |
| adverse event  Date of  onset:  Was the event serious?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | Yes                                                                                                                                                         | No                      |      |       |        |        |          |        |       |      |       |
| If yes, please state the criteria for seriousness below:  Serious event criteria (tick all that apply): Death Life threatening  Hospitalisation/prolonged existing hospitalisation Persistent/significant incapacity/disability  Congenital anomaly/birth defect Medically important event Status on the date of  reporting or of death:  Resolution }  Resolution with sequelae }  Resolution ongoing  Not resolved Unknown Is there a reasonable possibility that the event may have been  linked to a study medication? Yes No If yes, please state the study medication: |                                                                                                                                                             |                         |      |       |        |        |          |        |       |      |       |
| Date                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | of                                                                                                                                                          |                         |      |       |        |        |          |        |       |      |       |
| resolution:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | Date                                                                                                                                                        | of                      |      |       |        |        |          |        |       |      |       |
| resolution:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  |                                                                                                                                                             |                         |      |       |        |        |          |        |       |      |       |
| Is there a reasonable possibility that the event may have been  linked to a concomitant medication? Yes No If yes, please state the concomitant medication:                                                                                                                                                                                                                                                                                                                                                                                                                  | Is there a reasonable possibility that the event may have been  linked to a concomitant medication? Yes No If yes, please state the concomitant medication: |                         |      |       |        |        |          |        |       |      |       |
| Last step taken in response to the event(s); please state  medication name:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | Last step taken in response to the event(s); please state  medication name:                                                                                 |                         |      |       |        |        |          |        |       |      |       |  
Page 89 of 90 Study medication Concomitant medication Study medication *Concomitant medication*  
  
|                                                                                                                                                                                                                                                                          | Stopped (temporarily or   |                              |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|------------------------------|
| permanently,                                                                                                                                                                                                                                                             | or                        |                              |
| administration deferred)  Dose reduced   Dose increased   No change to dose  Unknown  None taken                                                                                                                                                                         |                           | Stopped (temporarily or      |
| permanently,                                                                                                                                                                                                                                                             | or                        |                              |
| administration deferred)  Dose reduced   Dose increased   No change to dose  Unknown  None taken                                                                                                                                                                         |                           |                              |
| Did an AE/SAE develop again on reintroduction of the  medication?  Yes No Unknown Not applicable  If yes, which medication?   Stopped (temporarily or  permanently, or  administration deferred)  Dose reduced   Dose increased   No change to dose  Unknown  None taken |                           | Stopped (temporarily o       |
| permanently,                                                                                                                                                                                                                                                             | o                         |                              |
| administration deferred)  Dose reduced   Dose increased   No change to dose  Unknown  None taken                                                                                                                                                                         |                           |                              |
| Did an AE/SAE develop again on reintroduction of the medication?  Yes No Unknown Not applicable  If yes, which medication?                                                                                                                                               |                           |                              |
| Version 5 0_FR, August 2016                                                                                                                                                                                                                                              | Page ___ of ___           | Confidential Pfizer/Novartis |  
PROTOCOL/STUDY NUMBER SITE NUMBER PATIENT IDENTITY NUMBER
0 0 0 0 0 0 0 0  
  
Description of the event State all information not given elsewhere on the form relating to the circumstances, chronology, diagnosis and treatment of the event(s). If more space is needed, use copies of this page.  
Reporter's comments:  
| Reporter:                                                                                                                          |                                                            | -                                        | -                |         |
|------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------|------------------------------------------|------------------|---------|
|                                                                                                                                    | First name                                                 | Surname (Please write in BLOCK CAPITALS) | Date: DD-MM-YYYY |         |
| Address:                                                                                                                           |                                                            | /                                        |                  |         |
|                                                                                                                                    | Street                                                     | Town                                     | Postcode         | Country |
| Telephone:                                                                                                                         | Fax:                                                       | Email:                                   |                  |         |
| Name                                                                                                                               | of                                                         | participating                            | doctor:          |         |
| __________________________________                                                                                                 | Signature of participating doctor/doctor's representative: |                                          |                  |         |
| Date participating doctor/representative became aware of the event:                                                                | -                                                          | -                                        | DD-MM-YYYY       |         |
| Send this form to Pfizer within 24 hours of becoming aware of the event or immediately in the event of death or a life-threatening |                                                            |                                          |                  |         |  
Send this form to Pfizer within 24 hours of becoming aware of the event or immediately in the event of death or a life-threatening SAE.  
INCLUDE ALL RELEVANT INFORMATION ON THE FORM. DO NOT ATTACH SOURCE DOCUMENTS.  
Version 5 0_FR, August 2016 Page ___ of ___ Confidential Pfizer/Novartis