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Trial record 3 of 3 for:    small cell lung cancer BMN 673

Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors

This study has been withdrawn prior to enrollment.
(The pharmaceutical company did not want to follow through with support for the study.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02537561
First Posted: September 1, 2015
Last Update Posted: February 11, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
In this proposed study the investigators will combine gemcitabine and cisplatin with talazoparib to determine the recommended Phase 2 dose (RP2D) of this combination regimen. After determination of the RP2D patients with lung cancer whose tumors carry molecular alterations in DNA repair pathway genes will be enrolled to an expansion cohort to determine anti-tumor efficacy. Tissue samples of patients with confirmed partial response, complete response, and non-responders will be obtained for whole exome, and transcriptome sequencing to characterize the genetic alterations associated with response to therapy.

Condition Intervention Phase
Solid Tumors Carcinoma, Non-Small Cell Lung Non-Small Cell Lung Cancer Non-Small-Cell Lung Carcinoma Nonsmall Cell Lung Cancer Drug: Cisplatin Drug: Gemcitabine Drug: Talazoparib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Adaptive Design Trial of Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: 30 days after completion of treatment (estimated average to be 7 months) ]
  • Maximum tolerated dose (MTD) [ Time Frame: Completion of dose escalation portion of study (approximately 12 months) ]
    The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 30% of patients in a cohort are expected to experience a dose-limiting toxicity (DLT) during the second cycle based on the CRM algorithm. Dose escalations will proceed until the MTD is determined.

  • Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype [ Time Frame: Up to completion of treatment (estimated average of 6 months) ]
    ORR - proportion of patients who achieved a complete response or a partial response


Secondary Outcome Measures:
  • Disease control rate (DCR) [ Time Frame: Until death (estimated average to be 12 months) ]
    • DCR - percentage of participants who have achieved complete response, partial response, and stable disease
    • Complete response: disappearance of all lesions and normalization of tumor marker level
    • Partial response: at least a 30% decrease in the sum of the diameters of target lesions and no new lesions
    • Stable disease: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease

  • Progression-free survival (PFS) [ Time Frame: Until death (estimated average to be 12 months) ]

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    -Progressive disease - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one more new lesions PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.


  • Objective response rate (ORR) [ Time Frame: Up to completion of treatment (estimated average of 6 months) ]
    ORR - proportion of patients who achieved a complete response or a partial response

  • Overall survival (OS) [ Time Frame: Until death (estimated average to be 12 months) ]
    OS: duration of time from start of treatment to time of death from any cause


Enrollment: 0
Study Start Date: December 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors
  • Dose levels of the drugs will be dependent on which dose level the participants is enrolled.
  • Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
  • Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
  • Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
  • Cisplatin and gemcitabine will be given for a total of 6 cycles.
  • Talazoparib may be continued as a single agent maintenance therapy.
Drug: Cisplatin
Other Names:
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • DDP
Drug: Gemcitabine
Other Name: Gemzar®
Drug: Talazoparib
Other Name: BMN 673
Experimental: Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC
  • Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study
  • Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
  • Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
  • Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
  • Cisplatin and gemcitabine will be given for a total of 6 cycles.
  • Talazoparib may be continued as a single agent maintenance therapy.
Drug: Cisplatin
Other Names:
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • DDP
Drug: Gemcitabine
Other Name: Gemzar®
Drug: Talazoparib
Other Name: BMN 673

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of advanced solid tumor for which no curative standard treatment options exist and for which gemcitabine and cisplatin is a suitable treatment regimen.
  • After the determination of the maximum tolerated dose, an expansion cohort of 20 patients with non-small cell lung cancer whose tumors demonstrate variants in DNA repair pathway genes will be enrolled.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • Prior treatment for this disease is allowed if it has been completed at least 2 weeks prior to study enrollment and if all treatment-related toxicities are resolved. Prior exposure to a PARP inhibitor is allowed for patients in the dose-finding portion of the study.
  • At least 18 years of age.
  • ECOG performance status ≤ 1
  • Normal bone marrow and organ function as defined below:

    • Leukocytes ≥ 3,000/mcL
    • Absolute neutrophil count ≥ 1,500/mcl
    • Platelets ≥ 100,000/mcl
    • Total bilirubin ≤ 1.5 x IULN
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
    • Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
    • Tissue available for sequencing (either archival tissue or readily accessible tumor for fresh routine biopsy).
    • Able to swallow tablets.
    • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
    • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Received any other investigational agent within 2 weeks of starting the first dose on study.
  • Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated. Patients must be at least 4 weeks post-brain radiation therapy.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine, talazoparib, or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active coronary artery disease, uncontrolled seizure, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Known HIV-positivity.
  Contacts and Locations
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): NCT02537561


Sponsors and Collaborators
Washington University School of Medicine
BioMarin Pharmaceutical
Investigators
Principal Investigator: Saiama Waqar, M.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02537561     History of Changes
Other Study ID Numbers: 15-x279
First Submitted: August 28, 2015
First Posted: September 1, 2015
Last Update Posted: February 11, 2016
Last Verified: February 2016

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Bronchial Neoplasms
Talazoparib
Carcinoma
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors