Clinical Trials /

Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer

NCT03377556

Description:

This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer
  • Official Title: A Phase II Study of Talazoparib (BMN 673) in Patients With Homologous Recombination Repair Deficiency Positive Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

Clinical Trial IDs

  • ORG STUDY ID: S1400G
  • SECONDARY ID: NCI-2017-00135
  • SECONDARY ID: S1400G
  • SECONDARY ID: S1400G
  • SECONDARY ID: S1400G
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03377556

Conditions

  • ATM Gene Mutation
  • ATR Gene Mutation
  • BARD1 Gene Mutation
  • BRCA1 Gene Mutation
  • BRCA2 Gene Mutation
  • BRIP1 Gene Mutation
  • CHEK1 Gene Mutation
  • CHEK2 Gene Mutation
  • FANCA Gene Mutation
  • FANCC Gene Mutation
  • FANCD2 Gene Mutation
  • FANCF Gene Mutation
  • FANCM Gene Mutation
  • NBN Gene Mutation
  • PALB2 Gene Mutation
  • RAD51 Gene Mutation
  • RAD51B Gene Mutation
  • RAD54L Gene Mutation
  • Recurrent Squamous Cell Lung Carcinoma
  • RPA1 Gene Mutation
  • Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

DrugSynonymsArms
TalazoparibBMN 673, BMN-673Treatment (talazoparib)

Purpose

This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the overall response rate (ORR) (confirmed and unconfirmed, complete and
      partial) with talazoparib (BMN 673) in HRRD Medivation (MDVN)-positive patients.

      SECONDARY OBJECTIVES:

      I. To evaluate investigator assessed progression-free survival (IA-PFS) and overall survival
      (OS) associated with therapy in HRRD MDVN-positive patients.

      II. To evaluate ORR, IA-PFS, and OS in HRRD Foundation Medicine, Inc. (FMI)-positive
      patients.

      III. To evaluate ORR in HRRD MDVN-negative/HRRD FMI-positive patients. IV. To evaluate the
      frequency and severity of toxicities associated with talazoparib (BMN 673) in HRRD
      FMI-positive patients.

      TERTIARY OBJECTIVES:

      I. To assess if the homologous recombination deficiency (HRD) score is associated with
      clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated with talazoparib
      (BMN 673).

      II. To assess if the level of PARP protein expression determined by immunohistochemistry is
      associated with clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated
      with talazoparib (BMN 673).

      III. To characterize pharmacokinetic properties of talazoparib (BMN 673).

      OUTLINE:

      Patients receive talazoparib orally (PO) once daily (QD) on days 1-21. Courses repeat every
      21 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 6 months for 2 years, and at the end of year 3.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talazoparib)ExperimentalPatients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON
             ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master
             Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)

          -  Patients must be assigned to S1400G; S1400G biomarker eligibility defined as
             homologous recombination repair deficiency (HRRD) positive is as follows

               -  Biomarker-positive group

                    -  HRRD by FMI

                         -  Homologous recombination repair deficiency by Foundation Medicine Inc.,
                            criteria

               -  Alteration type

                    -  Truncating mutation, frameshift deletions, indels missense and nonsense
                       mutations predicted to have functional consequence in any of the specified
                       genes

               -  Eligible alteration

                    -  Mutation in any one of the following critical HRR pathway genes: ATM, ATR,
                       BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF,
                       FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1

          -  Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g.,
             veliparib, olaparib, rucaparib, niraparib, talazoparib [BMN 673]) as its primary
             pharmacology

          -  Patients must have achieved stable disease, a partial response, or a complete response
             at their first disease assessment after initiating first-line platinum-based
             chemotherapy; patients determined to have progressed (in the opinion of the treating
             physician) at their first disease assessment are not eligible

          -  Patients may not have any impairment of gastrointestinal function or gastrointestinal
             disease that may significantly alter the absorption of talazoparib (BMN 673) (e.g.,
             ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
             small bowel resection, or active peptic ulcer disease); patients must not have active
             small or large intestine inflammation such as Crohn's disease or ulcerative colitis
             (within 12 months of sub-study registration)

          -  Patients must be able to take oral medications; patients must be able to swallow
             capsules whole without crushing or altering them in any way

          -  Patients must not be taking, nor plan to take while on protocol treatment strong
             P-glycoprotein (P-gp) inhibitors, P-gp inducers, or breast cancer resistance protein
             (BCRP) inhibitors; the language ?P-gp or BCRP inhibitors or inducers? is reworded to
             ?strong P-gp inhibitors, P-gp inducers, or BCRP inhibitors? for consistency with the
             investigator brochure

          -  Patients must agree to have blood specimens submitted for pharmacokinetic analysis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate assessed by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2)
Time Frame:Up to 3 years
Safety Issue:
Description:Primary analyses will be performed using a more restricted definition of homologous recombination repair deficiency (HRRD) -positivity (Medivation [MDVN] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). With 40 HRRD subset positive patients, overall response rate can be estimated within 13% with 95% confidence.

Secondary Outcome Measures

Measure:Duration of response (Design #2)
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.
Measure:Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #2)
Time Frame:Up to 3 years
Safety Issue:
Description:With 40 HRRD subset positive patients, toxicity rates can be estimated within 16% with 95% confidence. With 60 eligible patients, toxicity rates can be estimated within 13% with 95% confidence.
Measure:Median investigator assessed progression-free survival (IA-PFS) (Design #2)
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.
Measure:Overall survival (OS) (Design #2)
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

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