Clinical Trials /

Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial

NCT03990896

Description:

This research is to evaluate the effectiveness of Talazoparib as a potential treatment for metastatic breast cancer with a BRCA 1 or BRCA 2 mutation.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial
  • Official Title: Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial

Clinical Trial IDs

  • ORG STUDY ID: 19-188
  • NCT ID: NCT03990896

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TalazoparibTalzennaTalazoparib

Purpose

This research is to evaluate the effectiveness of Talazoparib as a potential treatment for metastatic breast cancer with a BRCA 1 or BRCA 2 mutation.

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The U.S. Food and Drug Administration (FDA) has not approved talazoparib for your specific
      disease but it has been approved for metastatic breast cancer with a germline (inherited)
      BRCA mutation.

      Talazoparib is a study drug that inhibits (stops) the normal activity of certain proteins
      called "poly (ADP-ribose) polymerases" also called "PARPs". PARPs are proteins (made from
      genes which are part of your DNA) that are found in all normal and cancer cells that are
      involved in the repair of DNA. PARPs are needed to repair mistakes that can happen in DNA
      when cells divide. If the mistakes are not repaired, the defective cell will usually die and
      be replaced. Cells with mistakes in their DNA that do not die can become cancer cells. Cancer
      cells may be killed by a study drug, like talazoparib, that stops the normal activity of
      PARPs. In clinical trials, the use of talazoparib and other PARP inhibitors have shown that
      these drugs can reduce tumor size and slow tumor growth in some cancer patients with BRCA1 or
      BRCA2 mutations.

      In this research study, the investigators are examining how effective talazoparib is in
      patients with metastatic breast cancer with a BRCA mutation in their tumor.
    

Trial Arms

NameTypeDescriptionInterventions
TalazoparibExperimental-Talazoparib will be provided as capsules for oral administration daily
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic breast cancer with deleterious somatic BRCA 1 or 2 mutations detectable by
             cell-free circulating tumor DNA, by CLIA certified clinical assay (including but not
             restricted to MGH-Snapshot cfDNA assay, Guardant360, Foundation One). The eligibility
             of a given assay and/or BRCA mutation could be discussed with the primary investigator
             (Dr. Vidula) and senior investigator (Dr. Bardia), who will provide the final
             discretion.

          -  Patients with germline BRCA 1 or 2 mutations will not be eligible.

          -  Patients with only a VUS (Variant of Unknown Significance), or non-functional BRCA
             mutation, without a deleterious somatic BRCA 1 or 2 mutation will not be eligible.

          -  The following disease subtypes are eligible:

               -  Triple negative breast cancer (defined as ER < 1%, PR < 1%, HER2 negative, as per
                  ASCO CAP guidelines), with disease progression on at least one prior chemotherapy
                  regimen in the metastatic setting.

               -  Hormone receptor positive, HER2 negative disease with disease progression on at
                  least one prior endocrine therapy in the metastatic setting or be considered
                  inappropriate for endocrine therapy

          -  Patients must have evaluable or measurable disease.

          -  Any number of prior lines of therapy are allowed

          -  Patients may have received prior platinum based chemotherapy (0-1 prior platinum based
             therapy). However, the patient must not have progressed while on platinum treatment
             (any setting), or within 6 months after end of treatment (neoadjuvant and/or
             adjuvant).

          -  At least two weeks from last systemic therapy for breast cancer, with recovery of all
             treatment related toxicity to grade 1 or less. Subjects with ≤ Grade 2 neuropathy are
             an exception to this criterion.

          -  At least two weeks from last radiation therapy, with recovery of all treatment related
             toxicity to grade 1 or less.

             -≥ 18 years of age on day of signing informed consent.

          -  ECOG performance status of ≤2.

          -  Adequate organ function as defined in Table 1 within 10 days prior to treatment
             initiation.

          -  Adequate Organ Function Laboratory Values

          -  SYSTEM LABORATORY VALUE

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7
                  days of assessment)

          -  Renal

             --Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
             used in place of creatinine or CrCl) ≤1.5 X institutional upper limit of normal (ULN)
             OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

          -  Hepatic

               -  Serum total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤
                  institutional ULN for subjects with total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X institutional ULN OR ≤ 5 X institutional ULN
                  for subjects with liver metastases

          -  Prior CNS disease is allowed if stable for at least one month since whole brain
             radiation therapy in patients who received whole brain radiation, or 2 weeks since
             stereotactic radiotherapy in patients who received stereotactic radiotherapy. Patients
             should not be requiring steroids. Patients whose CNS disease was surgically treated
             may be enrolled if stable for at least one month after surgery, and not requiring
             steroids.

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication.
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required.

          -  Female subjects of childbearing potential must use an acceptable form of birth control
             per treating physician discretion or be surgically sterile, or abstain from
             heterosexual activity for the course of the study through 7 months after the last dose
             of study medication. Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 7 months after the last dose of study therapy.
             Additionally, male patients may not donate sperm during the duration of the study and
             through 7 months after the last dose of study therapy.

          -  Willing and able to provide written informed consent.

        Exclusion Criteria:

          -  Treatment with an investigational agent within 4 weeks of the first dose of treatment.

          -  Patients must not have received prior treatment with a PARP inhibitor

          -  Patients must not have a germline BRCA 1 or 2 mutation

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent. Note: Subjects
             with ≤ Grade 2 neuropathy are an exception to this criterion.

             --If subject received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has known, untreated central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 7 months
             after the last dose of trial treatment.

          -  Has a known history of Human Immunodeficiency Virus (HIV).

          -  Has known active Hepatitis B or Hepatitis C.

          -  Patients should not be on strong P-glycoprotein inhibitors.

          -  Patients should not be on any other anti-cancer therapy (chemotherapy, hormone
             therapy, immunotherapy, or alternate investigational therapy).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median Progression Free Survival
Time Frame:From the start of treatment until death or disease progression, up to approximately 2 years
Safety Issue:
Description:Progression-Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:From the start of treatment until treatment discontinuation, up to approximately 2 years
Safety Issue:
Description:The number of participants that achieve either a complete (CR) or partial response (PR) according to RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measure:Number of Participants with Treatment-related Serious Adverse Events
Time Frame:From the start of treatment until treatment discontinuation, up to approximately 2 years
Safety Issue:
Description:Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 5). The number of participants with grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Breast Cancer

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