Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT02393755|
Recruitment Status : Active, not recruiting
First Posted : March 19, 2015
Results First Posted : July 7, 2020
Last Update Posted : July 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Colon Adenocarcinoma Rectal Adenocarcinoma Recurrent Colon Carcinoma Recurrent Rectal Carcinoma Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer||Drug: Capecitabine Other: Laboratory Biomarker Analysis Drug: Nintedanib Other: Pharmacological Study||Phase 1 Phase 2|
- 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)
- 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 Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. (Phase II)
- IV. To assess the toxicity of dose regimen using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase II)
- I. Measurement of circulating angiogenic cytokines (CAFs): vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR) 1/2, placental growth factor (PlGF), granulocyte macrophage colony-stimulating factor (GMCSF), leptin, interleukin (IL)-1 alpha (a), IL-8, IL-6, fibroblast growth factor basic (FGFb), osteopontin and pentraxin-3. (Phase II)
- II. Measurement of drug levels and pharmacokinetic (PK)/pharmacodynamic (PD) modeling. (Phase II)
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer|
|Actual Study Start Date :||May 8, 2015|
|Actual Primary Completion Date :||November 1, 2017|
|Estimated Study Completion Date :||January 1, 2021|
Experimental: Treatment (capecitabine, nintedanib)
Patients 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Experimental: Treatment (capecitabine , nintendanib)
Patients receive the highest safe dose of the combination of nintedanib and capcitabine.
- To Examine the DLT [ Time Frame: At least 21 days. ]
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).
- Progression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II) [ Time Frame: At 18 weeks ]
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.
- Median PFS (Phase II) [ Time Frame: Up to 2 years ]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. Estimates of median PFS will be obtained with corresponding 90% confidence intervals.
- Median OS (Phase II) [ Time Frame: From the date of enrollment to the time of death, assessed up to 2 years ]Overall survival is defined as time from date of subject enrollment to the date of death due to any cause. Estimates of median OS will be obtained with corresponding 90% confidence intervals.
- Objective Response Rate [ Time Frame: After every 3 cycles (9 weeks) of therapy. ]Overall Response is defined as Complete Response: Disappearance of all target lesions and any lymph nodes must have a reduction in short axis to < 10 mm; or Partial Response: At least a 30% decrease in the sum of diameters of target lesions; or Stable Disease: Neither sufficient shrinkage to qualify for partial response, nor sufficient increase to qualify for progressive disease.
- Aggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II) [ Time Frame: Up to 30 days after the last dose of study drug ]Number of Participants with Adverse Events, Graded According to the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02393755
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Christos Fountzilas||Roswell Park Cancer Institute|