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

NCT02537561 | Withdrawn Phase 1

• 1 other identifier: 15-x279
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumors; Carcinoma, Non-Small Cell Lung; Nonsmall Cell Lung Cancer; Non-Small-Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  30 days after completion of treatment (estimated average to be 7 months)

• Maximum tolerated dose (MTD)

  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.

  Completion of dose escalation portion of study (approximately 12 months)

• Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype

  ORR - proportion of patients who achieved a complete response or a partial response

  Up to completion of treatment (estimated average of 6 months)

Secondary Outcomes (4)

• Disease control rate (DCR)

  Until death (estimated average to be 12 months)

• Progression-free survival (PFS)

  Until death (estimated average to be 12 months)

• Objective response rate (ORR)

  Up to completion of treatment (estimated average of 6 months)

• Overall survival (OS)

  Until death (estimated average to be 12 months)

Study Arms (2)

Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors

EXPERIMENTAL

* 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; Drug: Gemcitabine; Drug: Talazoparib

Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC

EXPERIMENTAL

* 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; Drug: Gemcitabine; Drug: Talazoparib

Interventions

Cisplatin DRUG

Also known as: cis-DDP, cis-Platinum II, cis-Diamminedichloroplatinum, DDP

Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors; Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC

Gemcitabine DRUG

Also known as: Gemzar®

Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors; Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC

Talazoparib DRUG

Also known as: BMN 673

Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors; Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• BioMarin Pharmaceutical: collaborator

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Gemcitabine; talazoparib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Saiama Waqar, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: December 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 11, 2016

Record last verified: 2016-02