A Blinded, Randomized, Phase 1/2 Study of Brivanib Alaninate vs. Placebo in Combination with Erbitux and Irinotecan in K-Ras wild type Subjects with Metastatic Colorectal Cancer. Revised Protocol 03 (v5.0, dated 2 July 2008) incorporating Protocol Amendment 04 (v1.0, dated 2 July 2008). And Pharmacogenetics Blood Sample Amendment 01.Estudio fase 1/2, enmascarado y aleatorizado de brivanib alaninato frente a placebo en combinación con Erbitux e Irinotecán en sujetos con cáncer colorrectal metastásico con K-Ras de tipo natural.Protocolo revisado 03 (v5.0, 02-Julio-08) incorporando la enmienda al protocolo 04(v1.0, 2 -Julio- 2008) y enmienda 01 de muestra de sangre para farmacogénética.

Phase 1

• Conditions: Patients with advanced metastatic colorectal cancer (MCRC)Pacientes con cáncer colorrectal metastásico avanzado; MedDRA version: 9.1Level: LLTClassification code 10061451Term: Colorectal cancer

• Registration Number: EUCTR2007-005097-31-ES
• Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-09-25
• Study Completion: 2012-12-21
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

1) Signed Written Informed Consent a) Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal subject care. 2) Target Population a) Able to comply with visits/procedures required by protocol. b) Life expectancy at least 3 months. c) Subjects with histological or cytological confirmed diagnosis of metastatic CRC. d) Part 1: Subjects who have progressive or refractory disease after treatment with one or more chemotherapy regimens. e) Part 2: Subjects who have progressive or refractory disease after treatment with only one chemotherapy regimen. f) Subjects who have bi-dimensionally measurable disease by CT or MRI g) Subjects in both parts of the study may have received a prior irinotecan or a prior Erbitux containing regimen, but they may not have received a prior regimen containing both irinotecan and Erbitux. h) Exactly one prior anti-angiogenesis therapy alone or as part of a multidrug regime is permitted i) ECOG performance status 0-1 (Appendix 3) j) Subject must be available for follow-up k)Archived tumor must be confirmed to be K-Ras wild type by means of mutation analysis performed on representative samples of diagnostic tumor tissue by a central reference laboratory. 3) Age and Sex a) Men and women, over age 18. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea = 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL). Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product
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) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to12 weeks after the last dose of investig product b) WOCBP using a prohibited contraceptive method c) Women who are pregnant or breastfeeding d) Women with a positive pregnancy test on enrollment or prior to investigational product administration e) Sexually active fertile men not using effective birth control if their partners are WOCBP 2) Target Disease Exceptions a) Subjects with known brain metastasis b) Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI 3) Medical History and Concurrent Diseases a) Subjects with implantable porta-cath devices or central venous access are allowed in this study, but catheter prophylaxis with low dose warfarin is not permitted. A 14 day wash out period after stopping warfarin prophylaxis is required prior to starting study treatment. b) Any history of thrombo-embolic disease requiring therapeutic anticoagulation c) Subjects with concomitant second malignancies (except non-melanoma skin cancers, in situ bladder or cervical cancers) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period d) Subjects with history of poor wound healing or non healing ulcers e) Uncontrolled or signif. cardiovascular disease including: • Myocardial infarction within 12 months • Uncontrolled angina within 12 months • Class III-IV New York Heart Association (NYHA) congestive heart failure • LVEF < 45% • Uncontrolled hypertension (Systolic BP > 150 and diastolic BP > 100 mmHg for 24 hours). BP must be below 150/100 mmHg at screening. • History of stroke, TIA, or other ischemic event • Valvular heart disease CTCAE Grade = 2 (asymptomatic; moderate regurgitation or stenosis by imaging). f) A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy g) Any psychiatric or other disorders such as dementia that would prohibit the subjects from understanding or rendering informed consent or from fully complying with protocol treatment and follow-up h) Inability to swallow tablets or any gastrointestinal disease that may impact the absorption of the drug (i.e. recent gastrointestinal surgery such as a whipple procedure, mal-absorption syndrome.) i) Subjects requiring the use of a feeding tube j) Inability to tolerate multiple blood sampling/or tolerate venous access k) Any other sound medical, psychiatric, and/or social reason as determined by the Investigator 4) Physical and Laboratory Test Findings a) Absolute neutrophil counts < 1,500/mm3, platelet count < 100,000/mm3, or hemoglobin < 9 g/dL. b) serum total bilirubin > 1.5 times the institutional upper limits of normal or ALT or AST > 2.5 times the institutional upper limits of normal (> 5 times IULN for subjects with documented liver metastases). c) serum creatinine > 1.5 times the institutional upper limits of normal or calculated creatinine clearance < 50 mL/min/1.73m2 d) Subjects who are positive for UGT1A1 genotype *28/*28 (TA7/TA7) 5) Allergies and Adverse Drug Reactions a) History of allergy to brivanib its drug class or related compounds 6) Prohibited Treatments and/or The

Study & Design

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