A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer
A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer
This phase I/II trial studies the side effects and best dose of nintedanib when given together with capecitabine and to see how well they work in treating patients with colorectal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also block the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nintedanib with capecitabine may be a better treatment for colorectal cancer.
PRIMARY OBJECTIVES:
SECONDARY OBJECTIVES:
TERTIARY OBJECTIVES:
OUTLINE: This is a phase I, dose-escalation study of nintedanib followed by a phase II study.
Patients receive capecitabine orally (PO) twice daily (BID) (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 28 days until resolution or satisfactory stabilization of persistent drug-related toxicity, and then every 6 months thereafter.
Inclusion Criteria:
Exclusion Criteria:
Prior treatment with nintedanib
Prior treatment with regorafenib
Major injuries or surgery within the 4 weeks prior to initiation of therapy with incomplete wound healing or planned surgery during the on-study treatment period
Uncontrolled hypertension: systolic blood pressure >= 160, diastolic blood pressure >= 90
Urine protein/creatinine ratio >= 1.0
History of clinically significant hemorrhagic or thrombotic event within the past 6 months, not including uncomplicated catheter-associated venous thrombosis; patients on anti-coagulation are not permitted to be on any oral formulations (warfarin, rivaroxaban, dabigatran, etc.) due to concern for drug-drug interaction
Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)
History of cerebrovascular or myocardial ischemia within 6 months of initiation
Known inherited predisposition to bleeding or thrombosis
Known active or chronic hepatitis B or C or human immunodeficiency virus (HIV)
Untreated brain metastases
History of second primary malignancy diagnosed within 3 years prior to enrollment, excluding:
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
Received an investigational agent within 4 weeks prior to enrollment
PHASE I: History of intolerance to capecitabine at doses =< 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome, documented severe diarrhea requiring hospitalization, or other documented severe adverse events (AEs) attributable to capecitabine
PHASE II: History of intolerance to capecitabine at doses below 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome; documented severe diarrhea requiring hospitalization; or other documented severe AEs attributable to capecitabine