Clinical Trials /

Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes

NCT02286687

Description:

This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, do not respond to treatment, or have spread to other parts of the body, and have alterations in the breast cancer, early onset (BRCA) genes. Talazoparib may cause tumor cells to die by blocking an enzyme that protects the tumor cells from damage.

Related Conditions:
  • Cancer
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the PARP Inhibitor BMN 673 in Advanced Cancer Patients With Somatic Alterations in BRCA1/2, Mutations/Deletions in PTEN or PTEN Loss, a Homologous Recombination Defect, Mutations/Deletions in Other BRCA Pathway Genes and Germline Mutation in BRCA1/2 (Not Breast or Ovarian Cancer)
  • Official Title: Phase II Study of the PARP Inhibitor BMN 673 (Talazoparib Tosylate) in Advanced Cancer Patients With Somatic Alterations in BRCA1/2, Mutations/Deletions in PTEN or PTEN Loss, a Homologous Recombination Defect, Mutations/Deletions in Other BRCA Pathway Genes and Germline Mutation in BRCA1/2 (Not Breast or Ovarian Cancer)

Clinical Trial IDs

  • ORG STUDY ID: 2013-0961
  • SECONDARY ID: NCI-2014-02494
  • NCT ID: NCT02286687

Conditions

  • Advanced Cancers

Interventions

DrugSynonymsArms
Talazoparib TosylateBMN 673Mutation of BRCA1 or BRCA 2

Purpose

The goal of this clinical research study is to learn if talazoparib can help to control advanced cancer in patients who have a specific type of alteration (a type of genetic change). The safety of this drug will also be studied. This is an investigational study. Talazoparib is not FDA-approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 150 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Drug Administration:

      If you are found to be eligible to take part in this study, you will take talazoparib
      capsules by mouth 1 time each day. You should take the study drug at about the same time
      every day with or without food.

      If you miss a dose, you should skip that dose and take your next dose as scheduled. If you
      vomit after taking the study drug, do not take another dose to make it up. Wait and take your
      next dose as scheduled.

      Study Visits:

      Each study cycle is 28 days.

      During Weeks 1 and 2 of Cycle 1:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  Blood (about 2 teaspoons) will be drawn for biomarker and genetic testing.

        -  During Week 1, urine will be collected for routine tests, including a pregnancy test if
           you can become pregnant.

      During Weeks 3 and 4 of Cycle 1:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  Blood (about 2 teaspoons) will be drawn for biomarker and genetic testing.

        -  During Week 3, depending on when you are enrolled, you will have a tumor biopsy for PD
           testing. The study doctor will discuss this with you.

      During Week 1 of Cycles 2 and beyond:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) and urine will be drawn for routine tests.

      During Weeks 2, 3, and 4 of Cycles 2-12:

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

        -  During Week 4 only, blood (about 2 teaspoons) will be drawn for biomarker and genetic
           testing.

      Every 8 weeks for 6 months and then every 12 weeks after that, you will have a CT or MRI scan
      to check the status of the disease. If the disease appears to get better, you will have a
      repeat scan within 4 weeks.

      Starting at Cycle 13:

        -  Every 4 weeks, blood (about 4 teaspoons) and urine will be collected for routine tests.
           °You can perform this test at your local doctor's office and the results will be sent to
           the study staff.

        -  Every 12 weeks, blood (about 2 teaspoons) will be drawn for biomarker and genetic
           testing.

        -  Every 12 weeks, if you can become pregnant, urine collected will also be used for a
           pregnancy test.

      Length of Treatment:

      You may continue taking the study drug for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      Your participation on this study will be over after 1 year of follow-up calls.

      End-of-Treatment Visit:

      Right after your last dose of study drug, you will have an end-of-treatment visit:

        -  You will have a physical exam.

        -  Blood (about 6 teaspoons) and urine will be drawn for routine tests and biomarker and
           DNA testing.

      Follow-Up Visit:

      About 30 days after your last dose of study drug:

        -  Blood (about 4 teaspoons) and urine will be collected for routine tests.

        -  Blood (about 2 teaspoons) will be drawn for and biomarker and DNA testing.

      Long Term Follow-Up:

      The study staff will call you to ask how you are doing every 12 weeks for up to 1 year. Each
      call should last about 5 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
Mutation of BRCA1 or BRCA 2ExperimentalParticipants have mutation of BRCA1 or BRCA 2. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate
Deletion of BRCA1 or BRCA2ExperimentalParticipants have deletion of BRCA1 or BRCA2. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate
Mutation/Deletion ATM,PALB2,MER11,RAD50,NBS1ExperimentalParticipants have mutation or deletion in ATM, PALB2, MER11, ARID1A, RAD50, NBS1, ATR; amplification of EMSY or Fanconi Anemia Genes. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate
Mutation/Deletion in PTEN or PTEN Loss by IHCExperimentalParticipants have mutation or deletion in PTEN, or PTEN Loss. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate
Myriad HRD Assay LOH ≥ 42 Homologous Recombination DefectsExperimentalParticipants have Myriad HRD assay LOH ≥ 42 homologous recombination defects. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate
Germline Mutation of BRCA 1/ BRCA 2(not breast/ovarian ca)ExperimentalParticipants have Germline mutations of BRCA 1 or BRCA 2 (not breast or ovarian cancer) Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
  • Talazoparib Tosylate

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with advanced or metastatic cancer that is refractory to standard therapy or
             has relapsed after standard therapy.

          2. Patients must have one of the following: somatic mutations or deletions in BRCA1 or
             BRCA2; genomic alterations in other BRCA pathway genes (subcohorts: a. ATM, b. PALB2,
             c. other genes, e.g. Fanconi Anemia genes, ARID1A, MER11, RAD50, NBS1, ATR;
             amplification of EMSY); or germline mutation in BRCA1 or BRCA 2 (not breast or ovarian
             cancer)

          3. Patients must be >/=18 years of age.

          4. Patients must have measurable disease by RECIST 1.1.

          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

          6. Adequate organ function as defined: absolute neutrophil count >/=1500/mL; platelets
             >/= 100,000/mL; hemoglobin >/= 9 g/dL (or >/=5.6mmol/L); serum creatinine </= 1.5 X
             ULN (or GFR >/= 60 ml/min for patients with creatinine >1.5xULN); serum total
             bilirubin </= 1.5 X ULN (direct bilirubin </=ULN if total bili > 1.5xULN); AST(SGOT)
             and ALT(SGPT) </= 2.5X ULN (or </=5xULN if liver mets); INR or PT </=1.5xULN unless
             subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
             range of intended use of anticoagulants; aPTT </=1.5xULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants

          7. Patients must be >/=4 weeks beyond treatment with any chemotherapy or other
             investigational therapy to include hormonal, biological, or targeted agents; or at
             least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter
             at the time of treatment initiation.

          8. Women of child-bearing potential MUST have a negative serum or urine HCG test unless
             prior tubal ligation (>/= 1 year before screening), total hysterectomy or menopause
             (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant
             or breastfeed while on this study. Sexually active patients must agree to use dual
             contraception for the duration of study participation and for 120 days after the last
             dose of talazoparib.

          9. Ability to understand and willingness to sign informed consent form prior to
             initiation of the study and any study procedures

         10. Patients need to have biopsiable disease to enroll on cohort 1-2. Patients eligible
             for Cohort 3 with a germline BRCA alteration can be enrolled even if they do not have
             biopsiable disease.

        Exclusion Criteria:

          1. Patients who are pregnant or breastfeeding;

          2. Prior treatment with a PARP inhibitor;

          3. Known Hepatitis B, Hepatitis C or HIV infection;

          4. Inability or unwillingness to swallow pills.

          5. Active infection requiring intravenous (IV) antibiotics or other uncontrolled
             intercurrent illness requiring hospitalization.

          6. Any medical condition or diagnosis that would likely impair absorption of an orally
             administered drug (e.g. gastrectomy, ileal bypass, chronic diarrhea, gastroparesis).

          7. Inability to comply with the study and follow-up procedures.

          8. History of CVA, myocardial infarction or unstable angina within the previous 6 months
             before starting therapy

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

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

         11. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless or clinical stability.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit of Talazoparib Tosylate
Time Frame:Every 8 weeks for 6 months
Safety Issue:
Description:Clinical benefit (CB) defined as any of the following, complete response, partial response, or stable disease for > 24 weeks by RECIST 1.1. Assessments performed using computed tomography (CT) or magnetic resonance imaging (MRI) scan every 8 weeks.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Advanced Cancers
  • Germline mutations
  • Metastatic cancer
  • Talazoparib Tosylate
  • BMN 673
  • Phone call

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