- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01004822
A Safety, Tolerability, And Pharmacokinetic Trial With CVX-241 In Patients With Advanced Solid Tumors
October 16, 2015 updated by: Pfizer
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
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
31
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85258
- Premiere Oncology of Arizona
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California
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Santa Monica,, California, United States, 90404
- Premiere Oncology, A Medical Corporation
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Active Drug
Weekly infusions of CVX-241 at specified doses
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0.3 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
1 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
3 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
6 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
12 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
15 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
18 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
25 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle.
Weekly infusions administered until progression or unacceptable toxicity develops.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: Stage 1: Baseline up to Day 28 (end of cycle 1)
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MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT).
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
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Stage 1: Baseline up to Day 28 (end of cycle 1)
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Recommended Phase 2 Dose (RP2D)
Time Frame: Stage 1: Baseline up to Day 28 (end of cycle 1)
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RP2D was the highest dose where 0 of 3 or less than (<2) out of 6 participants experience a DLT.
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
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Stage 1: Baseline up to Day 28 (end of cycle 1)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Stage 1: Baseline up to Week 4
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DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
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Stage 1: Baseline up to Week 4
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
Time Frame: Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39)
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Adverse event (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 pretreatment state.
AEs included SAEs and non-SAEs that occurred during the study.
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Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39)
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Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf]
Time Frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
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AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞)u for unbound drug.
It is obtained from AUC (0 - t)u plus AUC (t - ∞)u for unbound drug.
Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
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Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
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Maximum Observed Plasma Concentration (Cmax)
Time Frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
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Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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Minimum Observed Plasma Trough Concentration (Cmin)
Time Frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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Systemic Clearance (CL)
Time Frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Due to premature termination of the study, only certain exposure-related noncompartmental PK parameters were calculated.
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Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
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Plasma Decay Half-Life (t1/2)
Time Frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
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Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
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Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
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Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations
Time Frame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
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VEGF family consists of five glycoproteins known as VEGF-A, -B, -C, and -D, and placental growth factor (PlGF), which bind to three structurally similar receptor tyrosine kinases VEGFR1, VEGFR2, and VEGFR3.
The different ligands have distinctive binding specificities for each of the receptors.
In response to ligand binding, the VEGFRs activate distinct downstream signalling pathways.
VEGFR2 is expressed in the vasculature and is the key mediator of VEGF-induced angiogenesis.
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Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
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Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations
Time Frame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
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Angiopoietin-2 (Ang2) and a related protein, angiopoietin-1 (Ang1) are ligands of the endothelial cell receptor Tie-2, a receptor tyrosine kinase, and are known to mediate the angiogenesis process together with VEGF and other angiogenic regulators.
Ang1 stimulates the phosporylation of Tie-2, recruits pericytes to newly formed blood vessels, and promotes their maturation.
Ang2 competes with Ang1 for binding of Tie-2, promotes the dissociation of pericytes, and results in unstable blood vessels.
In the presence of VEGF and other angiogenic factors, endothelial cells in these unstable vessels proliferate and migrate to form new blood vessels.
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Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
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Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies
Time Frame: Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39)
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Results were summarized for overall study population as per planned analysis.
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Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39)
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Objective Response Rate - Percentage of Participants With Objective Response
Time Frame: Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39)
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Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.
All nodes, both target and non-target, must decrease to normal (short axis <10 mm).
No new lesions.
PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions.
The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.
No unequivocal progression of non-target disease.
No new lesions.
Stable disease was defined as not qualifying for CR, PR, and Progressive Disease.
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Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39)
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Participants WithTumor Response of CA-125 Epithelial Ovarian Cancer (EOC)/ Primary Peritoneal Cancer (PPC)
Time Frame: Stage 2 every cycle
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Participants with epithelial ovarian cancer or primary peritoneal cancer having CA-125 levels greater than 2x the upper limit of normal, 2 weeks prior to starting therapy were evaluated for CA-125 response and response is defined as a 50% decrease in CA-125 from a pre-treatment sample.
The response was confirmed and maintained for at least 28 days.
CA-125 response was calculated as intervening samples and the 28-day confirmatory sample must be less than or equal to (within assay variability of 10%) the previous sample Progression or recurrence based on serum CA-125 is defined according to the participants baseline levels.
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Stage 2 every cycle
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Participants With Reduction in Tumor Vascular Permeability: Blood Flow and Blood Volume as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
Time Frame: Stage 2 predose up to end of study
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DCE-MRI is a non-invasive method that provides a functional assessment of microvasculature.
The technique can measure changes in vascular permeability, extracellular, and extravascular and vascular volumes.
Based on its ability to detect vascular changes, DCE-MRI has recently been evaluated as a biomarker of drug efficacy in clinical trials of angiogenesis inhibitors.
Assessment of DCE-MRI started at the 3.0 mg/kg dose cohort.
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Stage 2 predose up to end of study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2010
Primary Completion (ACTUAL)
May 1, 2014
Study Completion (ACTUAL)
May 1, 2014
Study Registration Dates
First Submitted
October 28, 2009
First Submitted That Met QC Criteria
October 28, 2009
First Posted (ESTIMATE)
October 30, 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
Additional Relevant MeSH Terms
Other Study ID Numbers
- B1561001
- CVX-241-101 (OTHER: Alias Study Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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