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: July 22, 2015
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: aflibercept
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 ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions:Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions

  • Progression-free Survival (Bevacizumab- naïve Group) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Kaplan-Meier method will be used.Progression-free survival (Bevacizumab- naïve group)


  • Progression-free Survival (Bevacizumab-treated Group) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Kaplan-Meier method will be used. Progression-free survival (Bevacizumab-treated group)



Secondary Outcome Measures:
  • Overall Survival (Bevacizumab-naïve Group) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used. (Bevacizumab- naïve Group)

  • Overall Survival (Prior Bevacizumab Treated Group) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used (Bevacizumab-naïve Group)

  • 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 ]
  • Number of Participants With Response (Bevacizumab-naïve Group) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD;

    Stable disease for atleast 16 weeks


  • Overall Survival (Bevacizumab-treated Group) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used. (Bevacizumab-treated Group)

  • Overall Survival (Bevacizumab-treated Group) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used (Bevacizumab-treated Group)

  • Number of Participants With Response (Bevacizumab-treated Group) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD;

    Stable disease for atleast 16 weeks



Enrollment: 75
Study Start Date: October 2006
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive VEGF Trap (aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: aflibercept
Given intravenously
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
  • ziv-aflibercept

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
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically/cytologically confirmed metastatic colorectal metastatic cancer
  • measurable disease (at least 1 lesion accurately measured in at least 1 dimension (longest diameter) as>20mm with conventional techniques or as >10mm with spiral CT scan
  • >=4 weeks from major surgery
  • at least 1prior line of systemic therapy for metastatic disease. Prior treatment with anti-epidermal growth factor receptor inhibitors is allowed. Last dose >=4 weeks prior to randomization
  • Two cohorts: 1) bevacizumab naïveand; 2) bevacizumab treated
  • May have received prior thymidylate synthetase inhibitor concurrently with radiation as "radiation sensitizer". Last dose >=4 weeks prior to randomization
  • Prior radiation treatment >=4 weeks prior to randomization
  • Age>=18 years
  • Life expectancy >=3 months
  • ECOG<=2 (Karnofsky=60%)
  • leukocytes >3.0x10^9/L
  • absolute neutrophil count >1.5 x 10^9/L
  • platelets>75x10^9/L
  • INR <1.5 unless on warfarin
  • total bilirubin within 1.5xULN
  • AST/ALT≤2.5 X institution ULN
  • creatinine≤1.5xULN OR creatinine clearance >60mL/min/1.73m2 for patients with creatinine levels above1.5x institution limits
  • Urinalysis negative for protein OR 24h urine for protein <500 mg
  • full-dose anticoagulants with PT INR >1.5 eligible provided that: a) patient is therapeutic on stable dose of warfarin or low molecular weight heparin; b) patients on warfarin, the upper target for INR is <=3; c) no active bleeding/pathological condition carrying high bleeding risk
  • Eligibility of patients receiving medications known to affect activity/PK of VEGF Trap will be determined by PI
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of VEGF Trap therapy
  • Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

  • chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior to study entry
  • Other investigational agents concurrently
  • History of prior anti-angiogenic therapy other than bevacizumab
  • Evidence of CNS disease
  • Known hypersensitivity to Chinese hamster ovary cell products/other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical/biologic composition to other agents used in the study.
  • Serious/non-healing wound/ulcer/bone fracture
  • History of abdominal fistula/GI perforation/bowel obstruction/intraabdominal abscess within 28 days of treatment
  • major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
  • anticipation of need for major surgical procedures during study
  • core biopsy within 7 days prior to Day 1 therapy
  • Patients with clinically significant cardiovascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • PT INR >1.5 unless the patient is on full-dose warfarin
  • Use of thrombolytic agents within 1 month of study initiation
  • Significant Proteinuria (>500mg/24h): Urine protein should be screened by random urinalysis for protein. If dipstick positive (>1+), 24-hour urine protein should be obtained and if >500mg/24 h, patient will be excluded.
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study
  • Pregnant women
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for PK interactions with VEGF Trap
  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
Results First Received: March 27, 2015
Last Updated: July 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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 August 27, 2015