Safety and Effectiveness Study of Chemotherapy and Ziv-aflibercept to Treat Metastatic Colorectal Cancer

NCT01889680 | Withdrawn Phase 2

• 1 other identifier: NSABP FC-8
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

FC-8 is a Phase II, multi-center randomized study of a continuation regimen of 5-FU/LV with ziv-aflibercept or 5-FU/LV alone (control arm) following the induction regimen of mFOLFOX6 and ziv-aflibercept as first-line therapy for patients with metastatic colorectal cancer. The primary aim of the study is to determine the value of adding ziv-aflibercept to the continuation regimen of 5-FU/LV in improving progression-free survival (PFS) of patients with metastatic colorectal cancer who have achieved at least stable disease after induction therapy. The secondary aim is to determine the overall objective response rate (complete, partial or stable responses) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Conditions

Colorectal Cancer; Metastatic Colorectal Cancer

Keywords

colorectal cancer; metastatic colorectal cancer; ziv-aflibercept; NSABP

Outcome Measures

Primary Outcomes (1)

• The time to disease progression

  From start of study through 5 months

Secondary Outcomes (3)

• Measurement of disease status by continuous tumor measurement

  From start of study through end of therapy, approximately 1 to 3 years

• The frequency of adverse events

  From start of study through end of therapy, approximately 1 to 3 years

• The severity of adverse events

  From start of study through end of therapy, approximately 1 to 3 years

Study Arms (2)

Arm 1: 5-FU + LV

ACTIVE COMPARATOR

Patients receive mFOLFOX6 plus ziv-aflibercept every 14 days for 6 cycles (induction regimen), followed by 5-FU/LV every 14 days until disease progression (continuation regimen)

Drug: 5-FU; Drug: LV; Drug: mFOLFOX6

Arm 2: 5-FU + LV + ziv-aflibercept

EXPERIMENTAL

Patients receive mFOLFOX6 plus ziv-aflibercept every 14 days for 6 cycles (induction regimen), followed by 5-FU/LV plus ziv-aflibercept every 14 days until disease progression (continuation regimen)

Drug: 5-FU; Drug: LV; Drug: ziv-aflibercept; Drug: mFOLFOX6

Interventions

5-FU DRUG

400 mg/m2 IV bolus day 1 followed by 2400 mg/m2 continuous IV infusion over 46 hours (days 1 and 2) every 14 days until disease progression

Also known as: 5-fluorouracil

Arm 1: 5-FU + LV; Arm 2: 5-FU + LV + ziv-aflibercept

LV DRUG

400 mg/m2 IV day 1 every 14 days until disease progression

Also known as: leucovorin

Arm 1: 5-FU + LV; Arm 2: 5-FU + LV + ziv-aflibercept

ziv-aflibercept DRUG

4 mg/kg IV day 1 every 14 days for 6 cycles (induction regimen); 4 mg/kg IV day 1 every 14 days until disease progression (continuation regimen)

Arm 2: 5-FU + LV + ziv-aflibercept

mFOLFOX6 DRUG

5-FU 400 mg/m2 IV bolus plus leucovorin 400 mg/m2 IV plus oxaliplatin 85 mg/m2 IV on day 1 followed by 5-FU 2400 mg/m2 continuous IV infusion over 46 hours (days 1 and 2) every 14 days

Also known as: 5-FU plus leucovorin plus oxaliplatin

Arm 1: 5-FU + LV; Arm 2: 5-FU + LV + ziv-aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.
• There must be histologic confirmation of a diagnosis of colorectal adenocarcinoma.
• There must be documentation by PET/CT scan, CT scan, or MRI, that the patient has evidence of measurable metastatic disease per RECIST 1.1.
• Prior adjuvant therapy is allowed if the last administration was greater than or equal to 6 months prior to randomization into this study including prior adjuvant oxaliplatin.
• Patients who have received prior oxaliplatin therapy must have neuropathy recovery greater than or equal to grade 1 according to CTCAE v4.0
• At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3; Platelet count must be greater than or equal to 100,000/mm3; and Hemoglobin must be greater than or equal to 9 g/dL.
• The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: Total bilirubin must be less than or equal to 1.0 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis; Alkaline phosphatase must be less than or equal to 3 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis
• Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab. (If creatinine 1.0-1.5 x ULN, the creatinine clearance should be 60 mL/mn per Cockcroft-Gault formula.)
• A urine sample must be tested for proteinuria by dipstick method. Eligibility must be based on the most recent test result performed within 4 weeks prior to randomization. Urine dipstick must indicate 0-1+ protein and negative blood. If dipstick reading is greater than or equal to 1+ protein and greater than or equal to trace hematuria or greater than or equal to 2+ protein, a 24 hour urine specimen must be collected and must demonstrate less than or equal to 500 mg of protein.
• Patients with reproductive potential (male/female) must agree to use accepted and effective methods of contraception while receiving study therapy, and for at least 6 months after the completion of study therapy. (The definition of effective method of contraception will be based on the investigator's judgment.)

You may not qualify if:

• Diagnosis of anal or small bowel carcinoma.
• Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
• Previous therapy with ziv-aflibercept or other angiogenesis inhibitors for any malignancy.
• Previous chemotherapy or any other systemic therapy for metastatic colorectal cancer.
• Prior radiotherapy less than or equal to 28 days from study entry.
• Patients with initially resectable liver-only disease.
• Active hepatitis B or hepatitis C with abnormal liver function tests.
• History of brain metastases, uncontrolled spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Intrinsic lung disease resulting in dyspnea.
• Active infection or chronic infection requiring chronic suppressive antibiotics.
• Persistent CTCAE v4.0 greater than or equal to grade 2 diarrhea regardless of etiology.
• Uncontrolled high blood pressure defined as systolic BP greater than or equal to 150 mmHg or diastolic BP greater than or equal to 100 mmHg with or without anti-hypertensive medication. Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.
• Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
• CTCAE v4.0 grade 3 or 4 anorexia or nausea related to metastatic disease.
• History of hypertensive crisis or hypertensive encephalopathy.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Sanofi: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; aflibercept; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: June 28, 2013
• Study Start: November 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2018
• Last Updated: December 2, 2014

Record last verified: 2014-11