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

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

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).

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: CVX-060 + sunitinib; Drug: CVX-060 + sunitinib; Drug: CVX-060 + sunitinib; Drug: CVX-060 + sunitinib; Drug: Sunitinib

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Premiere Oncology of Arizona
  • California
    • Santa Monica, California, United States, 90404
      • Premiere Oncology, A Medical Corporation
  • Mississippi
    • Southaven, Mississippi, United States, 38671
      • Boston Baskin Cancer Foundation
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • Boston Baskin Cancer Foundation
    • Germantown, Tennessee, United States, 38138
      • Boston Baskin Cancer Foundation
    • Memphis, Tennessee, United States, 38120
      • Boston Baskin Cancer Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: September 22, 2009
• First Posted (Estimate): September 23, 2009

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Phase Ib Phase II Advanced solid tumor Clear cell renal cancer Sunitinib plus / minus CVX-060
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: B1131001; CVX-060-102 (Other Identifier: Alias Study Number); 2010-022657-42 (EudraCT Number)