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: May 16, 2014
Last verified: May 2014
  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 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 Adverse Events (AEs) and Serious Adverse Events (SAEs);Part I: Safety profile characterized by type, grade and frequency of all adverse events, [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

  • Part II: Progression free survival (PFS) in adult patients with previously treated mRCC. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs); Safety profile characterized by type, grade and frequency of all adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

  • Overall response rate (ORR) in mRCC patients treated with PF-04856884 in combination with AG013736 vs. AG013736 alone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Duration of response in mRCC patients treated with PF-04856884 in combination with AG013736 vs. AG013736 alone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters [Tmax (Time when maximum plasma concentration is reached)] will be estimated using noncompartmental methods. [ Time Frame: 0, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of study (expected ~6 months) ] [ Designated as safety issue: No ]
  • To determine if patients treated with PF 04856884 develop anti drug antibodies during their treatment with PF 04856884 [ Time Frame: 0 and 360 hours post dose and end of study (expected ~6 months) ] [ Designated as safety issue: No ]
  • Individual concentration/time data as well as change from baseline/time will be assessed for circulating pharmacodynamic and exploratory biomarkers. [ Time Frame: 0, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of study (expected ~6 months) ] [ Designated as safety issue: No ]
  • Part II: Progression free survival (PFS) in adult patients with previously treated mRCC as measured by an independent radiological assessment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) at two years in patients treated in protocol B1131004. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters [Cmax (Peak plasma concentration)] will be estimated using noncompartmental methods. [ Time Frame: 0, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of study (expected ~6 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters [Cmin (Minimum drug concentration)] will be estimated using noncompartmental methods. [ Time Frame: 0, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of study (expected ~6 months) ] [ Designated as safety issue: No ]

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
Pfizer Investigational Site
Scottsdale, Arizona, United States, 85258
Pfizer Investigational Site
Tucson, Arizona, United States, 85710
Pfizer Investigational Site
Tucson, Arizona, United States, 85704
United States, Colorado
Pfizer Investigational Site
Aurora, Colorado, United States, 80012
Pfizer Investigational Site
Boulder, Colorado, United States, 80303
Pfizer Investigational Site
Centennial, Colorado, United States, 80112
Pfizer Investigational Site
Colorado Springs, Colorado, United States, 80907
Pfizer Investigational Site
Colorado Springs, Colorado, United States, 80909
Pfizer Investigational Site
Denver, Colorado, United States, 80218
Pfizer Investigational Site
Denver, Colorado, United States, 80220
Pfizer Investigational Site
Lakewood, Colorado, United States, 80228
Pfizer Investigational Site
Littleton, Colorado, United States, 80120-4413
Pfizer Investigational Site
Lone Tree, Colorado, United States, 80124
Pfizer Investigational Site
Longmont, Colorado, United States, 80501
Pfizer Investigational Site
Parker, Colorado, United States, 80138
Pfizer Investigational Site
Pueblo, Colorado, United States, 81008
Pfizer Investigational Site
Thornton, Colorado, United States, 80260
United States, Nebraska
Pfizer Investigational Site
Omaha, Nebraska, United States, 68114
United States, Nevada
Pfizer Investigational Site
Henderson, Nevada, United States, 89014
Pfizer Investigational Site
Henderson, Nevada, United States, 89052
Pfizer Investigational Site
Henderson, Nevada, United States, 89074
Pfizer Investigational Site
Las Vegas, Nevada, United States, 89169
Pfizer Investigational Site
Las Vegas, Nevada, United States, 89148
Pfizer Investigational Site
Las Vegas, Nevada, United States, 89128
United States, North Carolina
Pfizer Investigational Site
Durham, North Carolina, United States, 27704
United States, Texas
Pfizer Investigational Site
Fort Worth, Texas, United States, 76177
Pfizer Investigational Site
Tyler, Texas, United States, 75702
United States, Washington
Pfizer Investigational Site
Seattle, Washington, United States, 98109
Pfizer Investigational Site
Seattle, Washington, United States, 98195
Czech Republic
Pfizer Investigational Site
Brno, Czech Republic, 65653
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01441414     History of Changes
Other Study ID Numbers: B1131004
Study First Received: August 26, 2011
Last Updated: May 16, 2014
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
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014