A RANDOMIZED, PHASE 2 STUDY OF FOLFOX OR FOLFIRI WITH AG-013736OR BEVACIZUMAB IN PATIENTS WITH METASTATIC COLORECTALCANCER AFTER FAILURE OF AN IRINOTECAN OR OXALIPLATINCONTAININGFIRST-LINE REGIMEN - ND

• Conditions: Axitinib (AG-013736) in combination with intravenous 5-fluorouracil-based chemotherapy isindicated for the second-line treatment of patients with metastatic carcinoma of colon andrectum.; MedDRA version: 9.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic

• Registration Number: EUCTR2007-006283-30-IT
• Lead Sponsor: PFIZER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-30
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 176

Inclusion Criteria

1. Histologically-documented metastatic CRC plus any one of the following:
Failure of one prior irinotecan- or oxaliplatin-containing regimen documented with radiographic evidence of disease progression as defined by RECIST criteria and
documented with 2 sets of CT/MRI scans during irinotecan or oxaliplatin therapy or within 6 months after the last dose of the irinotecan- or oxaliplatin-containing
regimen (patients with prior adjuvant chemotherapy or radiation therapy are eligible);
or
Intolerance to prior oxaliplatin therapy, defined as occurrence of Grade 3 or 4 neurotoxicity that is persistent between cycles.
2. Adequate organ function, as defined by the following criteria:
Absolute neutrophil count (ANC) >/= 1500 cells/mm3
Platelets >/=100,000 cells/mm3
Hemoglobin >/=9.0 g/dL
Total serum bilirubin AST and ALT abnormalities are due to underlying malignancy
Serum creatinine Urinary protein <1+ by urine dipstick. If dipstick is >/=1+ then a 24-hour urine collection should be done and the patient may enter only if urinary protein is
<2 grams per 24 hours
3. Measurable disease by RECIST. Measurable diseases that have been previously radiated
will not be considered target lesions unless an increase in size has been observed following completion of radiation therapy.
4. Male or female, >/=18 years of age
5. Life expectancy >/=12 weeks
6. ECOG performance status 0 or 1
7. Resolution of all acute toxic effects of prior radiotherapy (except for alopecia), or
surgical procedures to NCI CTCAE Grade elective surgery, study treatment should not be administered until surgical incision is
fully healed
8. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood
pressure readings taken at least 1 hour apart. The baseline systolic blood pressure
readings must be be are eligible.
9. Women of childbearing potential must have a negative serum or urine pregnancy test
within 3 days prior to treatment.
10. Signed and dated informed consent document indicating that the patient (or legally
acceptable representative) has been informed of all pertinent aspects of the trial before
enrollment.
11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures, including completion of PRO measures.
12. Eligible to receive FOLFIRI or FOLFOX in combination with bevacizumab
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior treatment of metastatic CRC with more than 1 systemic chemotherapy regimen for
metastatic disease. Patients who participated in study A4061020 are not eligible to
participate in this study.
2. Prior irradiation to >/=25% of the bone marrow (whole pelvis =25%; a patient with prior
whole pelvis irradiation is ineligible).
3. Pleural effusion or ascites that causes >/= Grade 2 dyspnea.
4. Current use or anticipated need for food or drugs that are known cytochrome P450 (CYP)
3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, itraconazole,
erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and
delavirdine) during the course of the study
5. Current use or anticipated need for drugs that are known CYP3A4 or CYP1A2 inducers
(i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,
primidone, rifabutin, rifampin, and St John's wort) during the course of study (Note: the
short-term use of dexamethasone as a premedication for chemotherapy is not an
exclusion criterion)
6. History of hemoptysis > œ tsp of bright red blood in one day within past 1 week.
7. Patients with active seizure disorder or brain metastases
8. Gastrointestinal abnormalities including:
inability to take oral medication
requirement for intravenous alimentation
prior surgical procedures affecting absorption including total gastric resection
treatment for active peptic ulcer disease in the past 6 months
active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis,
hematochezia or melena in the past 3 months without evidence of resolution
documented by endoscopy or colonoscopy
malabsorption syndromes
9. History of any second malignancy except those patients treated with curative intent for
skin cancer (other than melanoma) or in situ breast or cervical cancer, or those treated
with curative intent for any other cancer with no evidence of disease for 5 years.
10. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of
treatment. (Also excluded are patient with fine needle aspirations within 7 days of
treatment) Note: Insertion of a vascular access device is not considered major or minor
surgery.
11. Dementia or significantly altered mental status that would prohibit the understanding or
rendering of informed consent and compliance with the requirements of this protocol.
12. Any of the following within the 12 months prior to study drug administration: myocardial
infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic
congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein
thrombosis or pulmonary embolism.
13. Known dihydropyridine dehydrogenase deficiency.
14. History of hypersensitivity to 5-FU or LV.
15. Known human immunodeficiency virus (HIV) seropositivity or acquired
immunodeficiency syndrome (AIDS)-related illness.
16. Serious active infection (viral, fungal, bacterial). Infection requiring parenteral
antibiotics at time of enrollment will disqualify the patient.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified