A Phase Ib/ii, Multicenter, Trial Of Cvx-060, A Selective Angiopoietin-2 (Ang-2) Binding, Anti-angiogenic Covx-body, In Combination With Sunitinib In Patients With Advanced Renal Cell Carcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Pfizer
- Enrollment
- 34
- Locations
- 4
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study Overview
Brief Summary
The safety and tolerability of CVX-060 have been established in the first-in-human clinical trial, CVX-060-101. Thus, this phase Ib/II trial is to assess the safety and pharmacokinetics (PK) profiles of combining CVX-060 with sunitinib in patients with advanced solid tumors, and to subsequently assess the treatment efficacy of the combination treatment, as well as that of sunitinib alone in patients with advanced renal cell carcinoma (mRCC).
Detailed Description
On 23-Nov-2010, B1131001 (CVX-060-102) was closed to enrollment due to emerging clinical data which led to a re-assessment of the strategic goals of the PF-04856884 program. The study enrolled the Phase 1b portion only. Subsequently, on 25-Oct-2012, due to data safety signals in a separate clinical trial with PF-04856884 (CVX-060), all PF-04856884 studies were discontinued and ongoing patients on B1131001 were permitted to remain on study at a reduced PF-04856884 dose if determined to have been deriving clinical benefit.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed advanced/metastatic solid tumor
- •Having received at least 1 prior systemic therapy for the treatment of advanced/metastatic solid tumors
- •Histologically or cytologically confirmed renal cell carcinoma with clear cell histology and evidence of metastasis (No previous systemic therapy for the treatment of metastatic renal cell carcinoma)
- •Adequate laboratory tests
- •Eastern Cooperative Oncology Group (ECOG) 0-1, Life expectancy > or = 12 weeks and age > or = 18 years
Exclusion Criteria
- •Patients intolerant of prior anti-angiogenic agents
- •Recent history of bleeding or bleeding disorders
- •History of tumors in the brain
- •History of heart problems
- •History of severe allergic reaction to antibody therapy
Arms & Interventions
Cohort 1
CVX-060 + sunitinib
Intervention: CVX-060 + sunitinib (Drug)
Cohort 2
CVX-060 + sunitinib
Intervention: CVX-060 + sunitinib (Drug)
Cohort 3
CVX-060 + sunitinib
Intervention: CVX-060 + sunitinib (Drug)
Expanded cohort
CVX-060 + sunitinib
Intervention: CVX-060 + sunitinib (Drug)
Phase II - Arm A
CVX-060 + sunitinib
Intervention: CVX-060 + sunitinib (Drug)
Phase II - Arm B
sunitinib alone
Intervention: Sunitinib (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: Baseline up to Cycle 1( Day 1 to Day 42)
The MTD was defined as the dose level at which less than or equal to (\<=) 1/6 participants experienced Dose Limiting Toxicity (DLT) during the first cycle of treatment with the next higher dose having \>= 2/6 participants with DLT.
Progression-free Survival (PFS)
Time Frame: Baseline tumor progression/clinical deterioration or death (up to 28 days post last dose of study medication)
PFS was defined as the time from the first dose date to the first documentation of disease progression or death due to any cause, whichever occurred first.
Secondary Outcomes
- Pharmacokinetic Parameters of CVX-060(Pre-dose on Day 1 Cycle 1 ; post-dose on Day 1, 5, 8, 15, 22, 29 Cycle 1 , Day 1 Cycle 2, to Cycle 28 , end of study (7 days post last dose of study medication), follow-up visit (28 days post last dose of study medication))
- Number of Participants With Dose-limiting Toxicities (DLT)(Baseline up to 28 days post last dose of study medication)
- Serum Angiopoietin-2 (Ang-2) and Plasma Vascular Endothelial Growth Factor (VEGF) Levels(Ang-2 (Day 1, 2, 5, 8, 22, 29 Cycle 1, Day 1 Cycle 2 up to Cycle 28); VEGF (Day 1, 8, 15, 22 Cycle 1, Day 1 Cycle 2 up to Cycle 28))
- Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs)(Baseline up to 28 days post last dose of study medication)
- Percentage of Participants With Objective Response(Baseline up to 7 days post last dose of study medication)
- Duration of Response(Baseline up to 7 days post last dose of study medication)
- Number of Participants With Anti- CVX-060 Antibodies(Baseline up to 28 days after last CVX-060 dose)