Clinical Trials /

Pilot Study of Veliparib (ABT-888) and Lapatinib (Tykerb) in Patients With Metastatic, Triple Negative Breast Cancer

NCT02158507

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Veliparib (ABT-888) and Lapatinib (Tykerb) in Patients With Metastatic, Triple Negative Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: F131219003 (UAB 1372)
  • SECONDARY ID: 000504723
  • NCT ID: NCT02158507

Conditions

  • Metastatic Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Combination of Veliparib + LapatinibVeliparib (ABT-888), Lapatinib (Tykerb)Combination of Veliparib + Lapatinib

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Combination of Veliparib + LapatinibExperimentalLapatinib 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.
  • Combination of Veliparib + Lapatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must pathologically documented stage IV breast cancer.

          -  Tumor must be HER-2 negative, and estrogen and progesterone receptors negative.
             Patients with BRCA 1 or 2 mutations will not be included.

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension.

          -  Biopsy of a metastatic lesion is not required for protocol entry but all patients with
             reasonably accessible lesions must agree to biopsy. (Lung and brain metastasis will
             not be biopsied.) Patients with no reasonably accessible lesions can be enrolled in
             the trial.

          -  Prior Therapy:

               -  No more than two regimens in the metastatic setting as long as patients have
                  adequate performance status. Patients with no prior chemotherapy for metastatic
                  disease may be included in the trial if they received anthracyclines and taxanes
                  in the adjuvant or neoadjuvant settings. Chemotherapy naïve patients with
                  metastatic disease must have failed anthracyclines and taxanes.

               -  Chemotherapy treatment prior to enrollment must be discontinued for at least 3
                  weeks prior to study entry.

               -  Patients must have completed radiation therapy at least 21 days prior to
                  beginning protocol treatment.

          -  Patients must have recovered from all reversible toxicities related to prior therapy
             before beginning protocol treatment and may not have an pre- existing
             treatment-related toxicities higher than Grade 2. Patients must have less than Grade 2
             pre-existing peripheral neuropathy.

          -  Patients may receive bisphosphonates. However, if used, bone lesions may not be used
             for progression or response.

          -  At least 19 years of age.

          -  Life expectancy of >12 weeks.

          -  Performance status according to Eastern Cooperative Oncology Group (ECOG) is less than
             or equal to 2.

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count: greater than or equal to 1,000/uL

               -  Hemoglobin: greater than or equal to 9 mg/dL

               -  Platelets: greater than or equal to 100,000/uL

               -  Total bilirubin: less than or equal to 1.5 times the institutional upper limit of
                  normal

               -  AST (SGOT)/ALT (SGPT): less than or equal to 2.5 times the institutional upper
                  limit of normal without liver metastases OR less than or equal to 5 times the
                  institutional upper limit of normal if documented liver metastases

               -  Creatinine: less than or equal to 1.5 mg/dL OR calculated creatinine clearance
                  greater than or equal to 40 mL/min (calculated using the modified Cockcroft and
                  Gault method).

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Use of an effective means of contraception in subjects of child-bearing potential.

          -  Negative serum or urine beta-HCG (human chorionic gonadotropin) pregnancy test at
             screening for patients with childbearing potential.

          -  Ejection fraction must be 50%.

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents.

          -  No prior use of anthracyclines and taxanes for metastatic disease or in the adjuvant
             or neoadjuvant setting.

          -  Metastatic lesions identifiable only by PET.

          -  QTc (corrected QT) >470 msec. Excluded are patients who may develop prolongation of
             QTc. These conditions include patients with hypokalemia or hypomagnesemia, congenital
             long QT syndrome, patients taking anti- arrhythmic medicines or other medicinal
             products that lead to QT prolongation, and cumulative high-dose anthracycline therapy.

          -  Patients may not be receiving concurrent chemotherapy for treatment of metastatic
             disease.

          -  Active brain metastases: evidence of progression less than or equal to 3 months after
             local therapy. (Patients should be asymptomatic and off corticosteroids and
             anticonvulsants for at least 3 months prior to study entry).

          -  Patients with brain metastases must have at least one site of measurable disease
             outside of the central nervous system.

          -  Uncontrolled concurrent illness including, but not limited to, ongoing or active
             infection, history of recent myocardial infarction, symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Uncontrolled seizure disorder.

          -  Pregnant or lactating women are excluded. Because there is an unknown but potential
             risk for adverse events in nursing infants secondary to treatment of the mother,
             breastfeeding should be discontinued if the mother is treated. These potential risks
             may also apply to other agents used in this study.

          -  A prior invasive malignant disease within five years except for skin cancer (squamous
             cell or basal cell carcinoma).

          -  Patients with known history of HIV or Hepatitis B because of potential for added
             toxicity from treatment regimen.

          -  Dementia or altered mental status that would prohibit the understanding of informed
             consent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects experiencing study-related toxicities when taking Veliparib in Combination with Lapatinib
Time Frame:baseline to 4 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Complete responses plus partial responses will be included as indicators of an objective response rates.
Measure:Number of subjects with progression free survival (PFS) at 4 years after start of study.
Time Frame:Baseline to 4 years
Safety Issue:
Description:Number of subjects who survive to 4 years with no disease progression
Measure: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)
Safety Issue:
Description: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:Measure numbers of circulating tumor cells before and after therapy
Time Frame:Before and during Cycle 1 (consisting of 28 days)
Safety Issue:
Description: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.
Measure:Peak Plasma concentration of Veliparib and Palatinib when given in combination.
Time Frame:Throughout Cycle 1 up to day 10
Safety Issue:
Description: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:Measure level of the M30 before and after therapy
Time Frame:baseline to cycle 1
Safety Issue:
Description: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.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Alabama at Birmingham

Trial Keywords

  • metastatic
  • triple negative breast cancer (TNBC)
  • Veliparib
  • Lapatinib
  • estrogen receptor (ER) negative
  • progesterone receptor (PR) negative
  • human epidermal growth factor receptor 2 (HER-2-Neu) negative

Last Updated

December 28, 2016