Back to resultsPF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-04856884
Axitinib (AG-013736)
Axitinib (AG-013736)
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring CVX-060, PF-04856884, AG-013736, axitinib, mRCC, metastatic renal cell cancer, second line, anti-angiogenic, Ang-2
Eligibility Criteria
Inclusion Criteria:
- Adult male or female patients with histologically or cytologically confirmed renal cell cancer (RCC) with a component of clear cell subtype and evidence of metastasis
- Evidence of unidimensionally measurable disease
- Prior therapy: Part I: Having received 1 to 3 prior systemic regimens for treatment of mRCC
- Part II: Evidence of disease progression following 1 prior regimen administered as 1st line therapy for mRCC. The prior regimen must have contained one of the following: VEGFR2 tyrosine kinase inhibitor (TKI) or other anti VEGF [Vascular Endothelial Growth Factor] compounds, such as bevacizumab
- adequate bone marrow, liver and renal function
Exclusion Criteria:
Part I:
- Intolerant to prior AG 013736 therapy or prior treatment with compounds which contain the core platform antibody as PF 04856884
Part II:
- Prior AG 013736 therapy, more than one systemic first-line regimen for the treatment of mRCC and prior treatment with compounds which contain the core platform antibody as PF 04856884
- major surgery <4 weeks or radiation therapy <2 weeks prior to start of therapy
- clinically significant gastrointestinal abnormalities
- current use or anticipated need for drugs that are known potent CYP3A4 inhibitors and drugs that are known CYP3A4 or CYP1A2 inducers
- history of bleeding diathesis or coagulopathy
- Grade 3 or greater hemorrhage from any cause <4 weeks prior to screening;
- hemoptysis >½ teaspoon of blood per day within 2 weeks prior to screening.
Sites / Locations
- Pinnacle Oncology Hematology
- Arizona Oncology Associates, PC - HOPE
- Arizona Oncology Associates, PC-HOPE
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Rocky Mountain Cancer Centers
- Nebraska Methodist Hospital
- Comprehensive Cancer Centers of Nevada
- Comprehensive Cancer Centers of Nevada
- Comprehensive Cancer Centers of Nevada
- Comprehensive Cancer Centers of Nevada
- Comprehensive Cancer Centers of Nevada
- Comprehensive Cancer Centers of Nevada
- Regional Cancer Care-Durham
- Texas Oncology-Tyler
- Seattle Cancer Care Alliance
- University of Washington Medical Center
- Masarykuv onkologicky ustav
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ARM A
ARM B
Arm Description
PF-04856884 in combination with AG-013736
AG-013736 alone
Outcomes
Primary Outcome Measures
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall).
Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below.
Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Number of Participants With Serious Adverse Events (SAEs) in Part I
Incidence and severity of all-causality serious adverse events (SAEs) are presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week). Participants with treatment-related TEAE are coded as NA if they appear for the same preferred term under all-causality TEAE.
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) in Part II
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. Progression free survival was to be calculated as (first event date - the date of randomization +1).
Secondary Outcome Measures
Number of Participants With Non-serious AEs and SAEs
Incidence and severity of all-causality AEs and SAEs to be presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone.
ORR is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to all randomized participants as defined in the FA Set. Confirmed responses are those that persist on repeat imaging study ≥ 4 weeks after initial documentation of response. Participants who do not have on-study radiographic tumor evaluation or who die, progress, or drop out for any reason prior to reaching a CR or PR will be counted as non-responders (NR) in the assessment of ORR.
Duration of Response (DR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone
DR is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of tumor progression or to death due to cancer. Duration of tumor response was to be calculated as (the end date for DR - first CR or PR that is subsequently confirmed +1).
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached)
Pharmacokinetic parameter, Tmax (Time when maximum serum PF-04856884 concentration was reached) was done using non-compartmental methods.
Cmax (Observed Peak Serum PF-04856884 Concentration)
Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.
Cmin (Trough PF-04856884 Serum Concentration)
Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.
Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive
Detection of neutralizing anti-PF-04856884 antibodies was based on the ability of anti-PF-04856884 neutralizing antibodies to bind to Tag-PF-04856884.
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) as Measured by an Independent Radiological Assessment
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. PFS was to be calculated as (first event date - the date of randomization +1).
Overall Survival (OS) at 2 Years
OS is defined as the time from the first dose date to date of death. For participants not expiring, their survival times will be censored at the last date they are known to be alive, or 2 year whichever is earlier. The 2-year OS rate will be estimated from a time-to event analysis of OS.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01441414
Brief Title
PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma
Official Title
A PHASE II TRIAL OF PF-04856884 (CVX-060), A SELECTIVE ANGIOPOIETIN-2 (ANG-2) INHIBITOR IN COMBINATION WITH AG-013736 (AXITINIB) IN PATIENTS WITH PREVIOUSLY TREATED METASTATIC RENAL CELL CARCINOMA
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
November 21, 2011 (Actual)
Primary Completion Date
March 27, 2014 (Actual)
Study Completion Date
March 27, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the combination of PF-04856884 (CVX-060) in combination with Axitinib (AG-013736) in patients that have received one prior systemic regimen for metastatic renal cell carcinoma (mRCC) vs. axitinib alone.
Detailed Description
The study was prematurely discontinued on 06Nov2012 due to tolerability findings in patients treated in Part I of the study that have prompted the Sponsor to re-evaluate the strategic development of the program. An unexpected frequency of arterial thrombotic events (ATEs) and venous thrombotic events (VTEs) were reported in patients treated in Part I.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
CVX-060, PF-04856884, AG-013736, axitinib, mRCC, metastatic renal cell cancer, second line, anti-angiogenic, Ang-2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARM A
Arm Type
Experimental
Arm Description
PF-04856884 in combination with AG-013736
Arm Title
ARM B
Arm Type
Active Comparator
Arm Description
AG-013736 alone
Intervention Type
Biological
Intervention Name(s)
PF-04856884
Intervention Description
15 mg/kg/week intravenously [IV] until toxicity or disease progression
Intervention Type
Drug
Intervention Name(s)
Axitinib (AG-013736)
Intervention Description
5 mg PO BID
Intervention Type
Drug
Intervention Name(s)
Axitinib (AG-013736)
Intervention Description
5 mg PO BID
Primary Outcome Measure Information:
Title
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall).
Description
Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below.
Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Time Frame
4 months
Title
Number of Participants With Serious Adverse Events (SAEs) in Part I
Description
Incidence and severity of all-causality serious adverse events (SAEs) are presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week). Participants with treatment-related TEAE are coded as NA if they appear for the same preferred term under all-causality TEAE.
Time Frame
4 months
Title
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) in Part II
Description
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. Progression free survival was to be calculated as (first event date - the date of randomization +1).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Number of Participants With Non-serious AEs and SAEs
Description
Incidence and severity of all-causality AEs and SAEs to be presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Time Frame
3 years
Title
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone.
Description
ORR is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to all randomized participants as defined in the FA Set. Confirmed responses are those that persist on repeat imaging study ≥ 4 weeks after initial documentation of response. Participants who do not have on-study radiographic tumor evaluation or who die, progress, or drop out for any reason prior to reaching a CR or PR will be counted as non-responders (NR) in the assessment of ORR.
Time Frame
4 months
Title
Duration of Response (DR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone
Description
DR is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of tumor progression or to death due to cancer. Duration of tumor response was to be calculated as (the end date for DR - first CR or PR that is subsequently confirmed +1).
Time Frame
3 years
Title
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached)
Description
Pharmacokinetic parameter, Tmax (Time when maximum serum PF-04856884 concentration was reached) was done using non-compartmental methods.
Time Frame
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Title
Cmax (Observed Peak Serum PF-04856884 Concentration)
Description
Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.
Time Frame
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Title
Cmin (Trough PF-04856884 Serum Concentration)
Description
Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.
Time Frame
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Title
Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive
Description
Detection of neutralizing anti-PF-04856884 antibodies was based on the ability of anti-PF-04856884 neutralizing antibodies to bind to Tag-PF-04856884.
Time Frame
0 and 360 hours post dose and end of study
Title
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) as Measured by an Independent Radiological Assessment
Description
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. PFS was to be calculated as (first event date - the date of randomization +1).
Time Frame
3 years
Title
Overall Survival (OS) at 2 Years
Description
OS is defined as the time from the first dose date to date of death. For participants not expiring, their survival times will be censored at the last date they are known to be alive, or 2 year whichever is earlier. The 2-year OS rate will be estimated from a time-to event analysis of OS.
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female patients with histologically or cytologically confirmed renal cell cancer (RCC) with a component of clear cell subtype and evidence of metastasis
Evidence of unidimensionally measurable disease
Prior therapy: Part I: Having received 1 to 3 prior systemic regimens for treatment of mRCC
Part II: Evidence of disease progression following 1 prior regimen administered as 1st line therapy for mRCC. The prior regimen must have contained one of the following: VEGFR2 tyrosine kinase inhibitor (TKI) or other anti VEGF [Vascular Endothelial Growth Factor] compounds, such as bevacizumab
adequate bone marrow, liver and renal function
Exclusion Criteria:
Part I:
Intolerant to prior AG 013736 therapy or prior treatment with compounds which contain the core platform antibody as PF 04856884
Part II:
Prior AG 013736 therapy, more than one systemic first-line regimen for the treatment of mRCC and prior treatment with compounds which contain the core platform antibody as PF 04856884
major surgery <4 weeks or radiation therapy <2 weeks prior to start of therapy
clinically significant gastrointestinal abnormalities
current use or anticipated need for drugs that are known potent CYP3A4 inhibitors and drugs that are known CYP3A4 or CYP1A2 inducers
history of bleeding diathesis or coagulopathy
Grade 3 or greater hemorrhage from any cause <4 weeks prior to screening;
hemoptysis >½ teaspoon of blood per day within 2 weeks prior to screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Oncology Hematology
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Arizona Oncology Associates, PC - HOPE
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Arizona Oncology Associates, PC-HOPE
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80303
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80228
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Littleton
State/Province
Colorado
ZIP/Postal Code
80120-4413
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Lone Tree
State/Province
Colorado
ZIP/Postal Code
80124
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Longmont
State/Province
Colorado
ZIP/Postal Code
80501
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Parker
State/Province
Colorado
ZIP/Postal Code
80138
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Pueblo
State/Province
Colorado
ZIP/Postal Code
81008
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Thornton
State/Province
Colorado
ZIP/Postal Code
80260
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89014
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89074
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Regional Cancer Care-Durham
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27704
Country
United States
Facility Name
Texas Oncology-Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Masarykuv onkologicky ustav
City
Brno
ZIP/Postal Code
65653
Country
Czechia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1131004&StudyName=PF-04856884%20%28CVX-060%29%20In%20Combination%20With%20Axitinib%20In%20Patients%20With%20Previously%20Treated%20Metastatic%20Renal%20Cell%20Carcinoma
Description
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Learn more about this trial
PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma
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