Study comparing Tivozanib in combination with mFOLFOX6 against Bevacizumab in combination with mFOLFOX6 in patients with bowel cancer.

• Conditions: Metastatic colorectal cancer (CRC); MedDRA version: 14.1Level: PTClassification code 10010035Term: Colorectal cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-003502-24-BE
• Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-07
• Last Update Posted: 17 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

Subject is eligible for the study if all of the following apply:
1.) The subject, prior to any study-related procedures, has provided IRB/IEC approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for US sites).
2.) The subject is male or female, aged 18 years or older.
3.) The subject has histologically or cytologically confirmed mCRC for which bevacizumab/ mFOLFOX6 chemotherapy regimen would be the appropriate treatment per the investigator.
4.) The subject has at least one measurable lesion by RECIST Version 1.1. A lesion that has received prior radiotherapy may only be counted as a target lesion if it has progressed since radiotherapy as determined by PI or radiologist assessment.
5.) The subject has had no prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months.
6.) The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7.) Female subject must be either:
• post-menopausal (defined as women who are > 46 years of age and last menstrual period was more than 2 years ago) prior to Screening, or
• premanarchal prior to Screening, or
• documented surgically sterile or status post hysterectomy (at least 1 month prior to
Screening), or
• if of childbearing potential, must have a negative serum or urine pregnancy test at Screening. All females of childbearing potential who are sexually active will be required to use highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and throughout the study period and for 90 days after final study drug administration. Highly effective contraception is defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), or barrier methods of contraception including a condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
8.) Male subject and their female spouses/partners who are of childbearing potential and sexually active must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after final study drug administration. Highly effective contraception is defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), or barrier methods of contraception including a condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
9.) Female subject must not be breastfeeding at Screening or during the study period and for 90 days after final study drug administration.
10.) Female subject must not donate ova starting at Screening and throughout the study period and for 90 days after final study drug administration.
11.) Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after final study drug administration.
12.) Subject agrees not to participate in another investigational study while on study treatment.

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 126
F.1.3 Elderl

Exclusion Criteria

The subject has;
1. had any prior VEGF-directed therapy including VEGF antibody or any other agent or investigational agent targeting the VEGF pathway.
2. primary CNS malignancies or CNS metastases; subjects with previously treated brain metastases will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
3. any of the following hematologic abnormalities:
• Hemoglobin < 9.0 g/dL (90 g/L, 5.5854 mmol/L)
• ANC < 2000 per mm3
• Platelet count < 100,000 per mm3
• PT or PTT > 1.5 X ULN
4. any of the following serum chemistry abnormalities:
• Total bilirubin > 1.5 X ULN (or > 2.5 X ULN for subjects with Gilbert’s syndrome)
• AST or ALT > 2.5 X ULN (or > 5 X ULN for subjects with liver metastasis)
• Alkaline phosphatase > 2.5 X ULN (or > 5 X ULN for subjects with liver or bone metastasis)
• Serum albumin < 2.0 g/dL
• Creatinine > 1.5 X ULN (or calculated creatinine clearance < 60mL/min/1.73m2)
• Proteinuria > 2+ by urine dipstick; protein greater than 2+ must have 24-hour urine collection that is less than 2 gm/24hr
5. significant cardiovascular disease, including:
• History of clinically symptomatic left ventricular failure
• Uncontrolled hypertension: Systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart
• Hypertensive crisis or hypertensive encephalopathy within 6 months prior to administration of first dose of study drug
• Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug
• History of serious ventricular arrhythmia
• Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well-controlled with anti-arrhythmic medication)
• Significant structural or congenital heart disease
6. significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
• Deep vein thrombosis
• Pulmonary embolism
• Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
• Peripheral arterial ischemia > Grade 2
• Coronary or peripheral artery bypass graft
7. a non-healing wound, bone fracture, or skin ulcer.
8. inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug, or anticipation of major surgical procedure during the course of the study.
9. history of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks.
10. active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation.
11. history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
12. a serious/active infection or infection requiring antibiotics.
13. significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
• Hematemesis, hematochezia, melena or other gastrointestinal bleeding not directly attributable to mCRC > Grade 2. For subjects with gastrointestinal bleeds attributable to their underlying mCRC, this should be = Grade 3 at the time of study entry.
• Hemoptysi

Study & Design

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