Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer
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|ClinicalTrials.gov Identifier: NCT02451553|
Recruitment Status : Recruiting
First Posted : May 22, 2015
Last Update Posted : July 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Bile Duct Carcinoma Recurrent Malignant Solid Neoplasm Recurrent Pancreatic Carcinoma Stage III Pancreatic Cancer AJCC v6 and v7 Stage IVA Pancreatic Cancer Stage IVB Pancreatic Cancer||Drug: Afatinib Dimaleate Drug: Capecitabine Other: Laboratory Biomarker Analysis||Phase 1|
I. Evaluate the safety, maximum tolerated dose (MTD), and the recommended phase II dose (RP2D) of afatinib dimaleate (afatinib) in combination with capecitabine in patients with advanced solid tumors (phase I) and pancreatico-biliary cancers (phase Ib). (Phase I/Ib)
I. Evaluate biomarkers of response from tumor biopsies, including markers related to the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) pathways via OncoPlex or other equivalent gene sequencing assay. (Phase I/Ib)
II. Evaluate rates of response and stable disease, duration of response, time to progression, progression-free and overall survival. (Phase I/Ib)
OUTLINE: This is a phase I, dose-escalation study of afatinib dimaleate followed by a phase Ib study.
Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-21 and capecitabine PO twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/IB Multi-center Study of Irreversible EGFR/HER2 Tyrosine Kinase Inhibitor Afatinib (BIBW 2992) in Combination With Capecitabine for Advanced Solid Tumors and Pancretico-Biliary Cancers|
|Actual Study Start Date :||November 5, 2015|
|Estimated Primary Completion Date :||September 30, 2019|
|Estimated Study Completion Date :||September 30, 2020|
Experimental: Treatment (afatinib dimaleate, capecitabine)
Patients receive afatinib dimaleate PO QD on days 1-21 and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Afatinib Dimaleate
Other: Laboratory Biomarker Analysis
- Incidence of adverse events, assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days following the last dose of study treatment ]Adverse events will be tabulated and summarized by dose levels. Summary tabulations will be presented displaying the number of observations, mean, standard deviation, median, minimum, and maximum for continuous variables, and the number and percentage per category for categorical data. Toxicity measurement will be accompanied by 90% confidence intervals.
- Incidence of dose limiting toxicity (DLT) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase Ib) [ Time Frame: Up to 21 days ]DLTs will be tabulated and summarized by dose levels. Summary tabulations will be presented displaying the number of observations, mean, standard deviation, median, minimum, and maximum for continuous variables, and the number and percentage per category for categorical data. Toxicity measurement will be accompanied by 90% confidence intervals.
- Maximum tolerated dose (MTD) of afatinib dimaleate in combination with capecitabine (Phase Ib) [ Time Frame: Up to 21 days ]Defined as the dose at which 0/3 or =< 1/6 patients experience a DLT graded according to NCI CTCAE version 4.0, will be assessed.
- Recommended phase 2 dose (RP2D) (Phase Ib) [ Time Frame: Up to 3 years ]Defined as the best tolerated dose overall, considering overall toxicity, including beyond course 1, will be evaluated.
- Biomarker profile (including EGFR and HER2 gene copy number and mutations, Kirsten rat sarcoma viral oncogene homolog, B-Raf proto-oncogene, serine/threonine kinase, neuroblastoma RAS viral oncogene homolog NRAS mutations, and E-cadherin expression) [ Time Frame: Baseline ]Will be summarized using mean +/- standard deviation. Baseline biomarker profile will also be summarized by the categories of treatment responses. Logistic models with objective response and stable disease as outcome and the baseline tumor profile as covariate will be fitted to evaluate their association. Correlative analysis of the presence of specific biomarkers and objective response/stable disease and progression free survival (PFS) (for patients in expansion cohorts) will be performed using Chi-square test or Fisher?s exact tests, as appropriate.
- Duration of response [ Time Frame: Time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years ]Duration of response will be assessed with the Kaplan-Meier method.
- Duration of stable disease [ Time Frame: Time that stable disease is documented until the first date that recurrent disease is objectively documented, assessed up to 3 years ]Duration of stable disease will be assessed with the Kaplan-Meier method.
- Overall survival [ Time Frame: From the day of first treatment to the earlier of (1) death (from any cause) and (2) the last date of subject contact, assessed up to 3 years ]Overall survival will be assessed with the Kaplan-Meier method.
- Progression-free survival [ Time Frame: From time from registration to disease progression or death of any cause, assessed up to 3 years ]Assessed with the Kaplan-Meier method.
- Rates of response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Up to 3 years ]Response rates will be tabulated and summarized by dose levels. Response rate measurement will be accompanied by 90% confidence intervals.
- Stable disease, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to quality for progressive disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Up to 3 years ]Stable disease will be tabulated and summarized by dose levels.
- Time to progression [ Time Frame: From the study enrollment until the criteria for disease progression are met (or death occurs), assessed up to 3 years ]Time to progression will be assessed with the Kaplan-Meier method.
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): NCT02451553
|United States, Indiana|
|Indiana University/Melvin and Bren Simon Cancer Center||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Sandra Wilson 317-274-3512 email@example.com|
|Principal Investigator: Safi Shahda|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Elena G. Chiorean 206-288-6248 firstname.lastname@example.org|
|Principal Investigator: Elena G. Chiorean|
|Principal Investigator:||Elena Chiorean||Fred Hutch/University of Washington Cancer Consortium|