Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
- Registration Number
- NCT00741260
- Lead Sponsor
- Puma Biotechnology, Inc.
- Brief Summary
This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.
In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.
Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.
In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.
Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.
The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.
The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.
The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.
Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Neratinib and Capecitabine (Dose Group 2) Neratinib Neratinib 240 mg and Capecitabine 1500 mg/m\^2 Neratinib and Capecitabine (Dose Group 5) Capecitabine Neratinib 160 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine MTD (Dose Group 7) Neratinib Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib Neratinib and Capecitabine (Dose Level 1) Neratinib Neratinib 160 mg and Capecitabine 1500 mg/m\^2 Neratinib and Capecitabine (Dose Level 1) Capecitabine Neratinib 160 mg and Capecitabine 1500 mg/m\^2 Neratinib and Capecitabine (Dose Group 2) Capecitabine Neratinib 240 mg and Capecitabine 1500 mg/m\^2 Neratinib and Capecitabine (Dose Group 3) Neratinib Neratinib 240 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine (Dose Group 3) Capecitabine Neratinib 240 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine (Dose Group 5) Neratinib Neratinib 160 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine (Dose Group 4) Neratinib Neratinib 200 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine (Dose Group 4) Capecitabine Neratinib 200 mg and Capecitabine 2000 mg/m\^2 Neratinib and Capecitabine MTD (Dose Group 6) Neratinib Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib Neratinib and Capecitabine MTD (Dose Group 7) Capecitabine Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib Neratinib and Capecitabine MTD (Dose Group 6) Capecitabine Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities From first dose date to day 21 Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
Maximum Tolerated Dose (MTD) of Capecitabine From first dose date to day 21. MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
Maximum Tolerated Dose (MTD) of Neratinib From first dose date to day 21. MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
- Secondary Outcome Measures
Name Time Method Overall Response Rate From first dose date to progression or last tumor assessment, up to three years. Number of Subjects with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
Clinical Benefit Rate From first dose date to progression or last tumor assessment, up to three years. The percentage of subjects with Complete Response, Partial Response, or Stable Disease at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Duration of Response From start date of response to first PD/death, up to three years. Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date of recurrence or progressive disease (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
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Trial Locations
- Locations (37)
USA Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
Kootenai Cancer Center
🇺🇸Post Falls, Idaho, United States
The Care Group, LLC. dba Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Arena Oncology Associates, PC
🇺🇸Lake Success, New York, United States
Dayton Clinical Oncology Program
🇺🇸Dayton, Ohio, United States
Berks Hematology Oncology
🇺🇸West Reading, Pennsylvania, United States
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