PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01441414
First received: August 26, 2011
Last updated: December 11, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Biological: PF-04856884
Drug: Axitinib (AG-013736)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.

  • Cmin (Trough PF-04856884 Serum Concentration) [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.

  • Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive [ Time Frame: 0 and 360 hours post dose and end of study ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 18
Study Start Date: November 2011
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM A
PF-04856884 in combination with AG-013736
Biological: PF-04856884
15 mg/kg/week intravenously [IV] until toxicity or disease progression
Drug: Axitinib (AG-013736)
5 mg PO BID
Active Comparator: ARM B
AG-013736 alone
Drug: Axitinib (AG-013736)
5 mg PO BID

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441414

Locations
United States, Arizona
Pinnacle Oncology Hematology
Scottsdale, Arizona, United States, 85258
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States, 85704
Arizona Oncology Associates, PC-HOPE
Tucson, Arizona, United States, 85710
United States, Colorado
Rocky Mountain Cancer Centers
Aurora, Colorado, United States, 80012
Rocky Mountain Cancer Centers
Boulder, Colorado, United States, 80303
Rocky Mountain Cancer Centers
Centennial, Colorado, United States, 80112
Rocky Mountain Cancer Centers
Colorado Springs, Colorado, United States, 80907
Rocky Mountain Cancer Centers
Colorado Springs, Colorado, United States, 80909
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80220
Rocky Mountain Cancer Centers
Lakewood, Colorado, United States, 80228
Rocky Mountain Cancer Centers
Littleton, Colorado, United States, 80120-4413
Rocky Mountain Cancer Centers
Lone Tree, Colorado, United States, 80124
Rocky Mountain Cancer Centers
Longmont, Colorado, United States, 80501
Rocky Mountain Cancer Centers
Parker, Colorado, United States, 80138
Rocky Mountain Cancer Centers
Pueblo, Colorado, United States, 81008
Rocky Mountain Cancer Centers
Thornton, Colorado, United States, 80260
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, Nevada
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States, 89014
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States, 89052
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States, 89074
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89128
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89148
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, North Carolina
Regional Cancer Care-Durham
Durham, North Carolina, United States, 27704
United States, Texas
Investigational Products Center (IPC) (drug shipment only)
Fort Worth, Texas, United States, 76177
Texas Oncology-Tyler
Tyler, Texas, United States, 75702
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
Czech Republic
Masarykuv onkologicky ustav
Brno, Czech Republic, 65653
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01441414     History of Changes
Other Study ID Numbers: B1131004  2011-002190-33 
Study First Received: August 26, 2011
Results First Received: March 27, 2015
Last Updated: December 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
CVX-060
PF-04856884
AG-013736
axitinib
mRCC
metastatic renal cell cancer
second line
anti-angiogenic
Ang-2

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Axitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 27, 2016