Clinical trial NCT04033991: Study of Patients With Metastatic and/or Advanced Renal Cell Carcinoma, Treated With Sunitinib/Axitinib.
Official title: A Real World Retrospective Database Study of Patients Diagnosed With Metastatic and/or Advanced Renal Cell Carcinoma and Treated With Sunitinib and/or Axitinib in a Specialist United Kingdom Oncology Centre
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carcinoma
Renal Cell
Keywords: Carcinoma;
renal cell;
cancer;
kidney;
sunitinib;
axitinib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-07-26
Enrollment: 684
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Over the age of 18 years
2. Diagnosis of renal cell carcinoma
3. Treatment with sunitinib and/or axitinib
4. Timeframe: from database inception date (2002) until June 30, 2018.

Brief summary: Research Questions:

To understand the clinical outcomes of patients treated with sunitinib in first line and axitinib in second line in a real world setting as therapies for metastatic and/or advanced renal cell carcinoma (mRCC).

Primary Objective:

1. What is the progression free survival (PFS) of patients treated in first line with sunitinib, and stratified by Memorial Sloan-Kettering Cancer Center / International Metastatic Renal Cell Carcinoma Database Consortium (MSKCC/IMDC) risk category (favourable, intermediate, poor)?
2. What is the progression free survival (PFS) of patients treated in second line with axitinib, and stratified by MSKCC/IMDC risk category (favourable, intermediate, poor)?

Detailed description: Research Questions:

To understand the clinical outcomes of patients treated with sunitinib in first line and axitinib in second line in a real world setting as therapies for metastatic and/or advanced renal cell carcinoma (mRCC).

Primary Objective:

1. What is the progression free survival (PFS) of patients treated in first line with sunitinib, and stratified by Memorial Sloan-Kettering Cancer Center / International Metastatic Renal Cell Carcinoma Database Consortium (MSKCC/IMDC) risk category (favourable, intermediate, poor)?
2. What is the progression free survival (PFS) of patients treated in second line with axitinib, and stratified by MSKCC/IMDC risk category (favourable, intermediate, poor)?

Secondary Objectives:

First Line:

1. What is the overall survival (OS) of all patients in first line with sunitinib, and stratified by MSKCC risk (favourable, intermediate, poor)?
2. What is the duration of therapy with sunitinib in first line (using time to treatment discontinuation \[TTD\]) for all patients and stratified by MSKCC risk (favourable, intermediate, poor)
3. Objective response rate (ORR)
4. Duration of objective response (complete response \[CR\] or partial response \[PR\])
5. Examine factors that predict TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems

   1. Less than one year from time of diagnosis
   2. Karnovsky performance status less than 80%
   3. Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl)
   4. Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l)
   5. Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl)
   6. Platelets greater than the upper limit of normal (e.g. greater than 400 000)
   7. Lactate dehydrogenase greater than 1.5 times the upper limit of normal
   8. Fuhrmann grade of tumour
   9. Tumour subtype e.g. clear cell versus. non-clear cell
6. Safety and tolerability data reporting for first line sunitinib

Second line:

1. What is the OS of all patients in second line with axitinib, and stratified by MSKCC risk (favourable, intermediate, poor)?
2. What is the duration of therapy with axitinib in second line (using TTD) for all patients and stratified by MSKCC risk (favourable, intermediate, poor)
3. ORR
4. Duration of objective response (CR or PR)
5. Examine factors that predict duration of TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems

   1. Less than one year from time of diagnosis
   2. Karnovsky performance status less than 80%
   3. Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl)
   4. Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l)
   5. Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl)
   6. Platelets greater than the upper limit of normal (e.g. greater than 400 000)
   7. Lactate dehydrogenase greater than 1.5 times the upper limit of normal
   8. Fuhrmann grade of tumour
   9. Tumour subtype e.g. clear cell vs. non-clear cell
6. Safety and tolerability reporting for second line axitinib

The objectives listed below will also be assessed as exploratory analyses for various patient subgroups of interest, and will be conducted if sufficient numbers of patients are available:

1. Axitinib PFS and OS, as a second line therapy following sunitinib, pazopanib, or following other Tyrosine kinase inhibitors (e.g. sorafenib)
2. Axitinib PFS and OS as a third line therapy
3. Axitinib PFS and OS post-immunotherapy (IO), taking into consideration 2nd and 3rd therapy lines, following all IO therapy options, E.g. atezolizumab/bevacizumab, nivolumab/ipilumimab, nivolumab, interleukin-2
4. For the post-sunitinib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib?
5. For the post-pazopanib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib?
6. Is the duration of therapy on first line sunitinib and/or pazopanib related to duration of therapy for second line axitinib?

Eligibility criteria: Inclusion criteria

1. Over the age of 18 years
2. Diagnosis of renal cell carcinoma
3. Treatment with sunitinib and/or axitinib
4. Timeframe: from database inception date (2002) until June 30, 2018.

Exclusion criteria

Patients meeting any of the following criteria will not be included in the study:

1. Under the age of 18 years
2. Diagnosis other than renal cell carcinoma
3. No treatment with sunitinib and/or axitinib

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Progression Free Survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
timeFrame: From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Progression Free Survival (PFS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
timeFrame: From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Overall Survival (OS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
timeFrame: From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Overall Survival (OS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
timeFrame: From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Best Overall Response (BOR) for Complete Response (CR), Partial Response (PR), Stable Disease (SD), PD and Surgical CR as Per RECIST v 1.1
timeFrame: Start of treatment till BOR of CR, PR, PD, SD, Surgical CR, or death/initiation of new therapy, whichever occurred first; from 2002 to 30 June 2018, anytime in these 16 years (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Objective Response Rate (ORR)
timeFrame: From start of treatment until CR,PR,PD,death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16 years (from data retrieved and observed retrospectively for approximately 1.2 years)
measure: Duration of Response (DOR)
timeFrame: From date of first documented CR/PR until PD/death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16years (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Time to Treatment Discontinuation (TTD)
timeFrame: From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Time to Treatment Discontinuation (TTD): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
timeFrame: From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Time to Treatment Discontinuation (TTD): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
timeFrame: From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
measure: Durable Response Rate (DRR)
timeFrame: 6 months from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
Other outcomes:
measure: Number of Participants Who Started Systemic Therapy Within 1 Year of Diagnosis
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Karnofsky Performance Status (KPS) Less Than 80 Percent (%)
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Hemoglobin Less Than Lower Limit of Normal (LLN)
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Serum Calcium >Upper Limit of Normal (ULN), Neutrophil >ULN, Platelets >ULN and Lactate Dehydrogenase >1.5*ULN
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants Per Tumor Fuhrman Grades
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Tumor Subtype
timeFrame: Baseline (data retrieved and observed retrospectively for approximately 1.2 years)
measure: Number of Participants With Adverse Events
timeFrame: From start of treatment until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)
Locations:
city: London
country: United Kingdom
facility: Pfizer UK
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: