A Trial Of CVX-060, An Anti-Angiogenic COVX-Body, In Combination With Sunitinib In Patients With Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: CVX-060 + sunitinib
* Drug: CVX-060 + sunitinib
* Drug: CVX-060 + sunitinib
* Drug: CVX-060 + sunitinib
* Drug: CVX-060 + sunitinib
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>CVX-060 + sunitinib | Drug: CVX-060 + sunitinib<br>* CVX-060 weekly infusions at 6.0 mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: CVX-060 / Sutent;|
| Experimental: Cohort 2<br>CVX-060 + sunitinib | Drug: CVX-060 + sunitinib<br>* CVX-060 weekly infusions at 12.0 mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: CVX-060 / Sutent;|
| Experimental: Cohort 3<br>CVX-060 + sunitinib | Drug: CVX-060 + sunitinib<br>* CVX-060 weekly infusions at 15.0 mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: CVX-060 / Sutent;|
| Experimental: Expanded cohort<br>CVX-060 + sunitinib | Drug: CVX-060 + sunitinib<br>* CVX-060 weekly infusions at TBD mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: CVX-060 / Sutent;|
| Experimental: Phase II - Arm A<br>CVX-060 + sunitinib | Drug: CVX-060 + sunitinib<br>* CVX-060 weekly infusions at TBD mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: CVX-060 / Sutent;|
| Active Comparator: Phase II - Arm B<br>sunitinib alone | Drug: Sunitinib<br>* 50 mg sunitinib daily (4 out of 6 weeks)<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | 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. | Baseline up to Cycle 1( Day 1 to Day 42) | 
| Progression-free Survival (PFS) | 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. | Baseline tumor progression/clinical deterioration or death (up to 28 days post last dose of study medication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters of CVX-060 | Pharmacokinetic parameters Area under the Curve (AUC), Maximum Observed Serum Concentration (Cmax), Minimum Observed Serum Trough Concentration (Cmin), Clearance (CL), terminal elimination half life (t1/2) were planned to be analyzed. | 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) | DLT included grade 4 neutropenia of >= 3 day duration or with grade 4 neutropenia associated with fever; grade 4 thrombocytopenia for >= 3 consecutive days; Proteinuria of >=2 grams (g) per 24 hours; inability to resume to CVX-060 or sunitinib within 14 days of scheduled administration due to treatment related toxicity; any Grade 3 nonhematologic toxicity except nausea, vomiting, and diarrhea; Grade 3 nausea, vomiting, or diarrhea which persists for >=48 hours; Any >= Grade 4 non-hematologic toxicity; Any additional hematological or non-hematological toxicity for which dose reduction was required or for which patient was discontinued from the trial. | 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) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre treatment state. | Baseline up to 28 days post last dose of study medication | 
| Percentage of Participants With Objective Response | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as >= 30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. | Baseline up to 7 days post last dose of study medication | 
| Duration of Response | Duration of response is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. Participants last known to be progression free are censored at the date of the last objective disease assessment that verified lack of disease progression. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase Ib Phase II Advanced solid tumor Clear cell renal cancer Sunitinib plus / minus CVX-060