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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01889680
• Date of registration: 25/06/2013
• Prospective Registration: Yes
• Primary sponsor: NSABP Foundation Inc
• Public title: Safety and Effectiveness Study of Chemotherapy and Ziv-aflibercept to Treat Metastatic Colorectal Cancer
• Scientific title: A Randomized Phase II Trial of Induction Regimen With mFOLFOX6 and Ziv-aflibercept for First-line Therapy of Metastatic Colorectal Cancer Followed by Continuation Regimen With 5-FU/LV Alone or With Ziv-aflibercept Until Disease Progression
• Date of first enrolment: November 2014
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01889680
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Contacts

• Name: Norman Wolmark, MD
• Affiliation: NSABP Foundation Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.)

Exclusion Criteria

- 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.

- CTCAE v4.0 greater than or equal to grade 2 vomiting related to metastatic disease.

- Any of the following cardiac conditions: Documented New York Heart Association (NYHA)
Class III or IV congestive heart failure; Myocardial infarction within 6 months prior
to study entry; Unstable angina within 6 months prior to study entry; Symptomatic
arrhythmia

- Serious or non-healing wound, skin ulcer, or bone fracture.

- Known bleeding diathesis or coagulopathy, or requirement of therapeutic dose of
coumadin.

- History of transient ischemic attack (TIA) or cerebral vascular accident (CVA) within
180 days prior to randomization.

- History of symptomatic peripheral ischemia.

- History of arterial thrombotic event within 180 days prior to randomization.

- Gastroduodenal ulcer(s), erosive esophagitis, or gastritis determined by endoscopy to
be active within 90 days prior to randomization.

- Infectious or inflammatory bowel disease or diverticulitis.

- History of GI perforation within 180 days prior to randomization.

- Symptomatic interstitial lung disease or definitive evidence of interstitial lung
disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea
at rest requiring current continuous oxygen therapy.

- Any significant bleeding (greater than or equal to grade 3 CTCAE v4.0) not related to
the primary colorectal cancer (CRC) tumor within 180 days prior to randomization.

- Major surgical procedure, open biopsy, or significant traumatic injury within 42 days
prior to randomization.

- Other malignancies unless the patient is considered to be disease-free and has
completed therapy for the malignancy greater than or equal to 12 months prior to
study entry. Patients with the following cancers are eligible if diagnosed and
treated within the past 12 months: carcinoma in situ of the cervix, colorectal
carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of
the skin.

- Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human
immunodeficiency virus (HIV) disease requiring antiretroviral treatment.

- Patients with known Gilberts syndrome.

- History of hypersensitivity to fluoropyrimidines, or folic acid derivatives.

- Known dihydropyrimidine dehydrogenase deficiency.

- Symptomatic peripheral sensory neuropathy greater


Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Metastatic Colorectal Cancer

Colorectal Cancer

Intervention(s)

Drug: 5-FU

Drug: LV

Drug: ziv-aflibercept

Drug: mFOLFOX6

Primary Outcome(s)

The time to disease progression [Time Frame: From start of study through 5 months]

Secondary Outcome(s)

The frequency of adverse events [Time Frame: From start of study through end of therapy, approximately 1 to 3 years]

Measurement of disease status by continuous tumor measurement [Time Frame: From start of study through end of therapy, approximately 1 to 3 years]

The severity of adverse events [Time Frame: From start of study through end of therapy, approximately 1 to 3 years]

Secondary ID(s)

NSABP FC-8

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Sanofi