Pilot Study of Veliparib (ABT-888) and Lapatinib (Tykerb) in Patients With Metastatic, Triple Negative Breast Cancer
This study will evaluate the effectiveness and safety of the combination of two drugs, Veliparib and Lapatinib, given to participants with metastatic triple negative breast cancer that have undergone previous treatment. Veliparib is an investigational drug and has not been approved by the FDA while Lapatinib has been approved by the FDA for another type of breast cancer. All eligible participants will receive the study medications and not a placebo.
Metastatic Triple Negative Breast Cancer
Drug: Combination of Veliparib + Lapatinib
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Pilot Study of Veliparib (ABT-888) and Lapatinib (Tykerb) in Patients With Metastatic, Triple Negative (ER, PR, and HER-2 Negative) Breast Cancer|
- Number of subjects experiencing study-related toxicities when taking Veliparib in Combination with Lapatinib [ Time Frame: baseline to 4 years ] [ Designated as safety issue: Yes ]Drug related toxicities for the safety analysis are defined as: a) any grade 3 or 4 non-hematologic toxicity except alopecia and nausea which is not refractory to anti-emetics; b) failure to recover to baseline (except alopecia) after delaying the next dose by more than 14 days; c) grade 3 or 4 neutropenia complicated by fever equal to or greater than 38.50 degrees C or infection, or grade 4 neutropenia of a least 7 days duration; or d) grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. Toxicity evaluation of the patients enrolled in the trial will be done using the NCI Common Toxicity Criteria.
- Number of subjects with objective response rate (ORR) at 4 years post baseline (Complete responses [CRs] plus partial responses [PRs] [ Time Frame: 4 years post baseline ] [ Designated as safety issue: No ]Complete responses plus partial responses will be included as indicators of an objective response rates.
- Number of subjects with progression free survival (PFS) at 4 years after start of study. [ Time Frame: Baseline to 4 years ] [ Designated as safety issue: No ]Number of subjects who survive to 4 years with no disease progression
- DNA methylation and RNA transcriptome will be evaluated before and after therapy; baseline pattern will be compared with the post treatment pattern to identify markers of response or resistance. [ Time Frame: Within 4 weeks of baseline (treatment initiation) ] [ Designated as safety issue: No ]Analysis of the genomic data from tumors may allow us to identify if there is a gene or groups of genes that will be able to predict response or resistance to the research combination; in order to conduct the genomic evaluation it is necessary to correlate with clinical response. In addition, we will conduct IHC studies in order to analyze markers that will indicate us if the combination of the research agents inhibit the targets for which they were designed (H2AX, BRCA and EGFR); this data needs to be correlated with clinical data to see if the lab evaluations correlate with the response of the patient. In addition, we will evaluate by IHC markers of apoptosis that will indicate us if the combination of research agents was cytotoxic against the tumor cells ; this data needs to be correlated with clinical data to see if the lab evaluations correlate with the response of the patient.
- Measure numbers of circulating tumor cells before and after therapy [ Time Frame: Before and during Cycle 1 (consisting of 28 days) ] [ Designated as safety issue: No ]Circulating tumor cells will be measured before and after therapy and will indicate if the therapy is active against the tumor; a decrease in the number of the circulating tumor cells will indicate effectiveness of the combination.
- Peak Plasma concentration of Veliparib and Palatinib when given in combination. [ Time Frame: Throughout Cycle 1 up to day 10 ] [ Designated as safety issue: No ]
Blood samples for the first day will be collected 5 minutes before the start of therapy, 30 and 60 minutes after the first dose of Lapatinib and then 2, 4, 6, 8, and 24 hours after the start of Lapatinib. On day 2, Lapatinib and Veliparib will be given and samples will be taken 30 and 60 minutes after the first dose and then at 2, 4, 6, 8, and 24 hours. Additional blood samples will be taken on day 3, before the third day dose of the combined study drugs. The same schema will be followed on days 8, 9, and 10.
Each pharmacokinetic variable will be divided by dose groups for descriptive statistical analyses (mean, standard deviation, coefficient of variation, geometric mean, median, minimum and maximum per dose group).
- Measure level of the M30 before and after therapy [ Time Frame: baseline to cycle 1 ] [ Designated as safety issue: No ]Serum levels of the apoptosis protein M30 will be measured before and after therapy and will indicate if the therapy is active against the tumor; an increase in the level of M30 will indicate effectiveness of the combination.
|Study Start Date:||July 2014|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Combination of Veliparib + Lapatinib
Lapatinib will be administered as a tablet at a dosage of 1250 mg/day continuously for 28 days starting on Day 1 of each cycle. Veliparib will be administered as a capsule at a dosage of 200 mg every 12 hours for 28 days starting on Day 2 of each cycle. A cycle of therapy is defined as 28 days. Treatment is administered on an outpatient basis. Patient response will be evaluated every 8 weeks according to the current Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and performance of relevant scans and/or x-rays.
Drug: Combination of Veliparib + Lapatinib
Treatment cannot be in administered conjunction with other chemotherapy, targeted therapy, radiation therapy, or other investigational drugs.
Breast cancer is the most commonly diagnosed cancer in American women. Metastatic breast cancer remains incurable partially due to the lack of targeted therapy for selected subsets of patients. There are five distinct subsets of breast cancer with unique biological profiles. Triple negative breast cancer (TNBC) is a subset with special clinical interest because of its significant percentage of occurrence (10-20% of all breast cancer diagnoses) and its poor prognosis. With no defined targeted therapy to date, this study seeks to investigate a therapeutic strategy based on specific molecular abnormalities in the tumor cells of TNBC.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02158507
|Contact: Pam Dixon, RN, BSN, OCNfirstname.lastname@example.org|
|Contact: Valeria Caterinnichia, RN, BSN, OCN||205-934-5367||Val7@uab.edu|
|United States, Alabama|
|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator: Andres Forero, MD|
|Principal Investigator:||Andres Forero, MD||University of Alabama at Birmingham|