Clinical trial NCT02537561: Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
Official title: A Phase I Adaptive Design Trial of Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Solid Tumors
Carcinoma, Non-Small Cell Lung
Non-Small Cell Lung Cancer
Non-Small-Cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2015-09-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
timeFrame: 30 days after completion of treatment (estimated average to be 7 months)
measure: Maximum tolerated dose (MTD)
timeFrame: Completion of dose escalation portion of study (approximately 12 months)
measure: Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype
timeFrame: Up to completion of treatment (estimated average of 6 months)
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Until death (estimated average to be 12 months)
measure: Progression-free survival (PFS)
timeFrame: Until death (estimated average to be 12 months)
measure: Objective response rate (ORR)
timeFrame: Up to completion of treatment (estimated average of 6 months)
measure: Overall survival (OS)
timeFrame: Until death (estimated average to be 12 months)
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: Saiama Waqar, M.D.
role: PRINCIPAL_INVESTIGATOR
References: