Irinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: June 3, 2011
Last updated: September 10, 2012
Last verified: September 2012
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.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase II Study of Second-line Irinotecan Plus Brivanib, a Dual Tyrosine Inhibitor of VEGFR and FGFR, in Metastatic Colorectal Cancer Patients Enriched for Elevated Levels of Plasma FGF Following Progression on Bevacizumab-based Treatment
Primary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||September 2015 (Final data collection date for primary outcome measure)
Experimental: Brivanib + Irinotecan
Brivanib 800 mg orally daily Days 1-14, and Irinotecan intravenously 180 mg/m^2 on Day 1.
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.
Other Name: BMS-582664
180 mg/m^2 by vein on Day 1 of a 14 day cycle.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
- Inability to swallow tablets or untreated malabsorption syndrome.
- Pre-existing thyroid abnormality with thyroid function that can not be maintained in the normal range with medication.
- History of human immunodeficiency virus (HIV).
- Patients with centrally cavitating lung lesions.
- Known bleeding diathesis.
- Inability to comply with study and/or follow-up procedures.
- Patients with known glomerular nephritis.
- Patients with known polycythemia.
- Patients with known Gilbert's syndrome.
- Women with a positive pregnancy test.
- Patients with hyponatremia (sodium < 130 mmol/L).
- Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry).
- Baseline serum calcium < 8.4 mg/dL (calcium supplementation may be given to restore the serum calcium above this level prior to study entry).
- Baseline serum magnesium < 1.5 mg/dL (magnesium supplementation may be given to restore the serum magnesium above this level prior to study entry).
- Known or suspected history of allergy to brivanib or any agents given in association with this study.
- Prisoners or subjects who are involuntarily incarcerated. Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01367275
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Michael Overman, MD
||UT MD Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||June 3, 2011
||September 10, 2012
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Fibroblast Growth Factor
tyrosine kinase receptors
vascular endothelial growth factor receptors
fibroblast growth factor receptors
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 19, 2013
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Cystic, Mucinous, and Serous
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Phytogenic
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Molecular Mechanisms of Pharmacological Action