Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Launched by ROSWELL PARK CANCER INSTITUTE · Mar 13, 2015

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ClinConnect Summary

PRIMARY OBJECTIVES:

* I. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of nintedanib when administered with capecitabine within the study population and, establish the recommended phase II dose (RP2D). (Phase I)
* II. To assess progression free survival at 18 weeks. (Phase II)

SECONDARY OBJECTIVES:

* I. To assess median progression free survival. (Phase II)
* II. To assess median overall survival from the date of enrollment to the time of death will be documented. (Phase II)
* III. To assess the objective response rate as measured by Response Evalu...

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Eligibility criteria

• Inclusion Criteria:
• • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• • Hemoglobin \>= 9 g/dL
• • Absolute neutrophil count \>= 1500/mm\^3
• • Platelet count \>= 100,000/mm\^3
• • Creatinine =\< 1.5 upper limit of normal (ULN) AND creatinine clearance (CrCl) \> 50 mL/min by Cockcroft-Gault equation
• • Males = (140 -age (yrs) (body weight (kg)/(72) (serum creatinine) (mg/dL)
• • Females = 0.85 \* (140-age (yrs) (body weight (kg)/(72)(serum creatinine (mg/dL)
• • Bilirubin \< ULN
• • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 1.5 ULN if without liver metastases
• • AST/ALT =\< 2.5 x ULN if with liver metastases
• • Coagulation parameters: international normalized ratio (INR) =\< 2, prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.5 X institutional ULN
• • Have measurable disease per RECIST 1.1 criteria
• • Histologically or cytologically proven adenocarcinoma of the colon or rectum
• • Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients
• • Ability to swallow and retain oral medication
• • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for three months following completion of therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• 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:
• • In-situ cervical carcinoma
• • Superficial bladder cancer
• • Non-melanoma skin cancer
• • Stage I breast cancer
• • Low grade (Gleason =\< 6) localized prostate cancer
• • Any additional malignancy which has been in clinical remission for at least 1 year
• • 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