Clinical trial NCT01004822: A Safety, Tolerability, And Pharmacokinetic Trial With CVX-241 In Patients With Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Open-label, Dose-escalation, Safety, Pharmacokinetic, And Pharmacodynamic Study Of Cvx-241, A Selective Angiopoietin-2 And Vascular Endothelial Growth Factor Binding, Anti-angiogenic Covx-body, In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Treatment Non-Randomized Single Group Assignment Safety Study Neoplasms Carcinoma Cancer Malignancy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-10-30
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if CVX-241 (PF-05057459) is safe and tolerable when given as weekly infusions to adult patients with advanced solid tumors.

Detailed description: The study was prematurely discontinued on 14 September 2011 due to no significant pharmacological effects (safety/PD/efficacy) through 25 mg/kg cohort, the T1/2 based on VEGF binding was shorter than expected and the current and/or higher doses were not considered feasible for further development. There were no safety concerns associated with the decision to terminate the program/study.

Eligibility criteria: Inclusion Criteria:

* Confirmed solid tumors unresponsive to current therapy or for which there is no standard therapy.
* Stage 2 only: Histologically or cytologically documented EOC or PPC with \< or equal to 3 previous anti-cancer therapies, but at least 1 prior platinum containing regimen.
* Adequate coagulation, liver, and renal function.
* Candidate for Dynamic Contrast-Enhanced Magnetic Resonance Imaging \[DCE-MRI\] evaluation
* Eastern Cooperative Oncology Group \[ECOG\] performance status of 0 or 1

Exclusion Criteria:

* History of clinically significant toxicity to Vascular Endothelial Growth Factor \[VEGF\] inhibition.
* Evidence of bleeding problems.
* Uncontrolled hypertension.
* Patients with primary brain cancer and/or non-small cell lung cancer of squamous cell histology

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Stage 1: Baseline up to Day 28 (end of cycle 1)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Stage 1: Baseline up to Day 28 (end of cycle 1)
Secondary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Stage 1: Baseline up to Week 4
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf]
timeFrame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
measure: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
measure: Systemic Clearance (CL)
timeFrame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
measure: Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations
timeFrame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
measure: Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations
timeFrame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
measure: Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies
timeFrame: Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39)
measure: Objective Response Rate - Percentage of Participants With Objective Response
timeFrame: Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39)
measure: Participants WithTumor Response of CA-125 Epithelial Ovarian Cancer (EOC)/ Primary Peritoneal Cancer (PPC)
timeFrame: Stage 2 every cycle
measure: Participants With Reduction in Tumor Vascular Permeability: Blood Flow and Blood Volume as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
timeFrame: Stage 2 predose up to end of study
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Premiere Oncology of Arizona
state: Arizona
city: Santa Monica,
country: United States
facility: Premiere Oncology, A Medical Corporation
state: California
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: