Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer
A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer
3 other identifiers
interventional
42
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2015
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2015
CompletedFirst Posted
Study publicly available on registry
March 19, 2015
CompletedStudy Start
First participant enrolled
May 8, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2017
CompletedResults Posted
Study results publicly available
July 7, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
May 18, 2021
CompletedJuly 8, 2021
July 1, 2021
2.5 years
March 13, 2015
July 12, 2019
July 6, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
To Examine the DLT
The recommended Phase II dose is of the Nintedanib and Capecitabine combination is defined as the dose level that causes dose limiting toxicities (DLTs) in ≤ 1 out of 6 patients at highest dose level below the maximally administered dose. Capecitabine is fixed dose at 2000 mg/m2; while Nintedanib is evaluated at 150mg (dose level 1) and 200 mg (dose level 2).
At least 21 days.
Progression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II)
Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions (the sum must also demonstrate an absolute increase of at least 5 mm) or the appearance of new lesions. Will be summarized using standard Kaplan-Meier methods.
At 18 weeks
Secondary Outcomes (4)
Median PFS (Phase II)
Up to 2 years
Median OS (Phase II)
From the date of enrollment to the time of death, assessed up to 2 years
Objective Response Rate
After every 3 cycles (9 weeks) of therapy.
Aggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II)
Up to 30 days after the last dose of study drug
Study Arms (2)
Treatment (capecitabine, nintedanib)
EXPERIMENTALPatients received capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeated every 21 days in the absence of disease progression or unacceptable toxicity.
Treatment (capecitabine , nintendanib)
EXPERIMENTALPatients receive the highest safe dose of the combination of nintedanib and capcitabine.
Interventions
Given PO
Eligibility Criteria
You may qualify if:
- 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
- +2 more criteria
You may not qualify if:
- 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
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
- Boehringer Ingelheimcollaborator
- National Comprehensive Cancer Networkcollaborator
Study Sites (2)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Related Publications (1)
Boland PM, Ebos JML, Attwood K, Mastri M, Fountzilas C, Iyer RV, Banker C, Goey AKL, Bies R, Ma WW, Fakih M. A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer. JNCI Cancer Spectr. 2024 Apr 30;8(3):pkae017. doi: 10.1093/jncics/pkae017.
PMID: 38697618DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Administrator, Compliance - Clinical Research Services
- Organization
- Roswell Park Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Christos Fountzilas
Roswell Park Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2015
First Posted
March 19, 2015
Study Start
May 8, 2015
Primary Completion
November 1, 2017
Study Completion
May 18, 2021
Last Updated
July 8, 2021
Results First Posted
July 7, 2020
Record last verified: 2021-07