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Trial record 3 of 9 for:    S1400

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

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ClinicalTrials.gov Identifier: NCT03377556
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : April 20, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Talazoparib Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 7, 2017
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment (talazoparib)
Patients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Talazoparib
Given PO
Other Names:
  • BMN 673
  • BMN-673



Primary Outcome Measures :
  1. Overall response rate assessed by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2) [ Time Frame: Up to 3 years ]
    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 :
  1. Duration of response (Design #2) [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.

  2. 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 ]
    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.

  3. Median investigator assessed progression-free survival (IA-PFS) (Design #2) [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.

  4. Overall survival (OS) (Design #2) [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.


Other Outcome Measures:
  1. Homologous recombination deficiency (HRD) immunohistochemistry score [ Time Frame: Up to 3 years ]
    A logistic regression model will be used as both a continuous variable and categorized as high versus low. A Cox regression model will be used to assess associations with progression free survival and overall survival.

  2. PARP protein expression levels assessed by immunohistochemistry [ Time Frame: Up to 3 years ]
    A logistic regression model will be used to evaluate if HRD score (as both a continuous variable and categorized as high versus low) and PARP protein expression levels are associated with response. Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.



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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03377556


  Show 1116 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Vassiliki Papadimitrakopoulou Southwest Oncology Group

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT03377556     History of Changes
Other Study ID Numbers: S1400G
NCI-2017-00135 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1400G ( Other Identifier: SWOG )
S1400G ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents