Irinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF

NCT01367275 | Terminated Phase 2 Results

• 1 other identifier: 2010-0378
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if adding brivanib to irinotecan can help control the disease in patients with colorectal cancer that has spread. The safety of this drug combination will also be studied.

Conditions

Colorectal Cancer; Colorectal Adenocarcinoma

Keywords

colon; Colorectum; Colorectal Cancer; Plasma FGF; Colorectal adenocarcinoma; Bevacizumab; Brivanib; BMS-582664; Irinotecan; CPT-11; Camptosar; Fibroblast Growth Factor; bFGF; tyrosine kinase receptors; vascular endothelial growth factor receptors; VEGFR; fibroblast growth factor receptors; FGFR

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Median Progression-Free Survival (PFS)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Enrollment (baseline) to disease progression or death, followed each 14 day treatment then every 2 months,up to 100 week

Study Arms (1)

Brivanib + Irinotecan

EXPERIMENTAL

Brivanib 800 mg orally daily Days 1-14, and Irinotecan intravenously 180 mg/m\^2 on Day 1.

Drug: Brivanib; Drug: Irinotecan

Interventions

Brivanib DRUG

800 mg (4 x 200 mg tablets) self-administered orally at approximate same time each day on a continuous daily schedule Days 1-14 of 14 day cycle.

Also known as: BMS-582664

Brivanib + Irinotecan

Irinotecan DRUG

180 mg/m\^2 by vein on Day 1 of a 14 day cycle.

Also known as: CPT-11, Camptosar

Brivanib + Irinotecan

Eligibility Criteria

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

You may qualify if:

• Signed written Informed Consent.
• Patient must have progressed on front-line chemotherapy treatment containing bevacizumab for histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic. Progression is defined as either radiographic or clinical progression.
• Patient must have measurable lesions as defined by RECIST version 1.1 criteria.
• ECOG performance status 0-2.
• Known bFGF level performed by a CLIA-certified laboratory performed during or within 12 weeks of last bevacizumab treatment
• Enrollment in the "Assessment of Targeted Therapies Against Colorectal Cancer" (ATTACC) protocol 2009-0091.
• LVEF \> 50% measured by 2-D echocardiogram
• Bone marrow function defined as the following: An absolute neutrophil count (ANC) =/\>1,500/mcl; Platelets =/\>100,000/mcl; Hemoglobin =/\> 8.5 g/dl.
• Renal function defined as the following: Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN).
• Hepatic function defined as the following: Serum total bilirubin \< 1.5 x ULN; AST (SGOT), ALT (SGPT) and alkaline phosphatase =/\< 2.5 x ULN; Serum albumin =/\> 2.5 g/dl; If liver involvement, AST, ALT, and alkaline phosphatase =/\< 5.0 x ULN.
• International normalized ratio (INR) =/\< 2.3 or Prothrombin Time (PT) =/\< 6 seconds above control unless patient is currently receiving warfarin therapy for the treatment or prevention of venous thrombosis.
• Men and women, age =/\> 18 years.
• A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study \[and for up to 12 weeks after the last dose of study drug\] to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom.
• 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 study drug to minimize the risk of pregnancy. WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product.

You may not qualify if:

• Women who are pregnant or breastfeeding.
• Patients with brain metastases.
• Patients with resectable colorectal cancer or non-adenocarcinoma cancer of the colon or rectum.
• Patients who have had prior therapy with brivanib, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy.
• Recent (within 4 weeks of the first study drug administration), or planned participation in another experimental therapeutic drug study.
• Recent (within 4 weeks of the first study drug administration) infusion of bevacizumab therapy.
• Prior irinotecan chemotherapy.
• Prior full field radiotherapy =/\<4 weeks or limited field radiotherapy =/\<2 weeks prior to first study drug administration.
• Recent use (within 4 weeks of first study drug administration) of St. John's Wort.
• Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE (version 4.0) Grade 4 within 30 days prior to first study drug administration
• Patients with uncontrolled or significant cardiovascular disease including: i) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction \< 12 months prior to first study drug administration. ii) Class III-IV New York Heart Association (NYHA) congestive heart failure. iii) Uncontrolled hypertension (Systolic blood pressure \[BP\] \> 150 mmHg and diastolic BP \> 90 mmHg for 24 hours) despite optimal medical management. Blood pressure must be below 140/90 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 substrates should be changed to an alternative antihypertensive medication prior to first study drug administration. iv) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. v) QTc (Fridericia) prolongation \>450 msec. vi) Subjects with valvular heart disease =/\> CTCAE (Ver. 4.0) Gr 2. vii) Left ventricular ejection fraction (LVEF) \< 50%.
• Active infection, less than 7 days after completing systemic antibiotic therapy.
• History of non-healing wounds or ulcers, or bone fractures within 3 months prior to first study drug administration.
• Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 1 week from first dose of first study drug administration.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Website

MeSH Terms

Conditions

Colorectal Neoplasms; Acrocephalosyndactylia

Interventions

brivanib; Irinotecan

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; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

As a result of the drug sponsor closing study early, the accrual goal was not met and with the small number of participants enrolled no statistical analysis or conclusions was possible from the data.

Results Point of Contact

• Title: Dr. Michael Overman, Associate Professor, GI Medical Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2828

Study Officials

• Michael Overman, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 7, 2011
• Study Start: August 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 3, 2020
• Results First Posted: September 3, 2020

Record last verified: 2020-09

Locations

US (1)