Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

VEGF Trap in Treating Patients With Previously Treated Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00407654
First received: December 4, 2006
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

This phase II trial is studying how well VEGF Trap works in treating patients with previously treated metastatic colorectal cancer. VEGF Trap may stop the growth of colorectal cancer by blocking blood flow to the tumor.


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: ziv-aflibercept
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of VEGF Trap in Patients With Previously Treated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response (defined as partial or complete response as defined by the RECIST criteria) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Time to progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Time to progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Objective stable disease rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Response duration [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Toxicity assessed using NCI CTCAE v.3.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: October 2006
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: ziv-aflibercept
Given orally
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the response rate (complete and partial) in patients with previously treated metastatic colorectal cancer treated with VEGF Trap.

II. Determine the incidence of disease stabilization, in terms of 4-month progression-free survival, in patients treated with this drug.

SECONDARY OBJECTIVES:

I. Determine the median survival time of patients treated with this drug. II. Determine the 1-year survival rate and stable disease rate in patients treated with this drug.

III. Determine the response or stable disease duration in patients treated with this drug.

IV. Determine the toxicity of this drug in these patients. V. Determine the time to disease progression in patients treated with this drug.

VI. Determine if changes in free VEGF Trap levels correlate with response or toxicity.

OUTLINE: This is a multicenter, open-label study.

Patients are stratified according to prior bevacizumab treatment (yes vs no). Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection at the beginning of each course and at 60 days after completion of study treatment. Samples are analyzed by immunoenzyme techniques to determine the pharmacokinetics of VEGF Trap.

After completion of study treatment, patients are followed at 30 and 60 days and then every 3 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST/ALT =< 2.5 times ULN
  • Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min
  • Proteinuria =< 1+ by dipstick OR urine protein < 500 mg by 24-hour urine analysis
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within the past 28 days
  • At least 4 weeks since prior major surgical procedure or open biopsy
  • Histologically or cytologically confirmed colorectal cancer
  • No significant traumatic injury within the past 28 days
  • Recovered from prior therapy
  • Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1 dimension as >= 20 mm by conventional techniques or as >= 10 mm by spiral CT scan
  • No prior surgery, radiation therapy, or radiofrequency ablation to the measurable lesion
  • Has received >= 1 prior systemic chemotherapy for metastatic disease AND has documented radiological or clinical progression after the most recent therapy
  • No CNS disease, including primary brain tumor or brain metastasis
  • Life expectancy >= 3 months
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • No clinically significant cardiovascular disease, including, but not limited to, any of the following: Peripheral vascular disease within the past 6 months (i.e., limiting activities of daily living or the presence of resting pain), Deep vein thrombosis, pulmonary embolism, or other thromboembolic event within the past 6 months, Coronary artery bypass graft within the past 6 months, OR;
  • OR; Unstable angina pectoris or myocardial infarction within the past 6 months, New York Heart Association class III or IV congestive heart failure, Serious cardiac arrhythmia requiring medication, Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg OR systolic BP > 180 mm Hg (if diastolic BP < 90 mm Hg) within the past 3 months
  • No evidence of bleeding diathesis or coagulopathy
  • No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection, Psychiatric illness or social situation that would limit compliance with study requirements
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., evidence of tumor invading major vessels by CT scan or known varices)
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of allergic reactions to compounds of similar chemical or biologic composition to VEGF Trap or other agents used in this study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for >= 6 months after completion of study treatment
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), prior thymidylate synthetase inhibitor (e.g., fluorouracil or capecitabine) allowed as a radiosensitizer
  • At least 4 weeks since prior radiation therapy of local disease, disease progression must be documented afterwards
  • At least 4 weeks since other prior anticancer agents
  • At least 4 weeks since prior thrombolytic agents
  • At least 7 days since prior core biopsy
  • No prior antiangiogenic therapy (e.g., vascular endothelial growth factor tyrosine kinase inhibitor) other than bevacizumab
  • Prior anti-epidermal growth factor receptor inhibitors allowed
  • No other concurrent investigational agents
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent major surgery
  • Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin) allowed provided dose is stable
  • WBC >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 75,000/mm^3
  • INR =< 1.5 (=< 3 if on full-dose warfarin)
  • Metastatic disease
  • Concurrent antihypertensive medications allowed, unless dose and/or quantity has been increased within the past 2 weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00407654

Locations
Canada, Ontario
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Malcolm Moore University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00407654     History of Changes
Other Study ID Numbers: NCI-2009-00176, PHL-050, CDR0000518293, N01CM62203
Study First Received: December 4, 2006
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Rectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Endothelial Growth Factors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014