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Talazoparib and Low-Dose Temozolomide in Treating Patients with Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer

Trial Status: Active

This phase II trial studies how effective talazoparib and temozolomide are for treating patients with extensive-stage small cell lung cancer that has come back (relapsed) after an initial chemotherapy treatment. Talazoparib, a PARP inhibitor, may stop the growth of tumor cells by preventing them from repairing their DNA. Chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving talazoparib and temozolomide may work better in treating patients with extensive-stage small cell lung cancer than either one alone.

Inclusion Criteria

  • Able to provide informed consent.
  • Cytologically or histologically confirmed small cell lung cancer (SCLC) with extensive-stage disease. This includes all high-grade neuroendocrine cancers of the lung.
  • Relapsed (progressed within 6 months) or refractory (progressed during or within 4 weeks of completing 1st line platinum based regimen).
  • Participants that were previously treated for limited stage small cell lung cancer and have recurred are eligible.
  • Measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Archival or fresh tissue biopsy available for exploratory analyses. Archival tissue must be collected within the past 3 years from cycle 1 day 1 (C1D1). Fresh tissue must be collected within 30 days from C1D1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1.
  • Able to swallow the study drugs, has no known intolerance to study drugs or excipients, and able to comply with study requirements.
  • Female participants of childbearing potential must have a negative pregnancy test at screening and must agree to use a highly effective birth control method (defined in protocol) from the time of the first study drug treatment through 7 months after the last study drug treatment.
  • Male participants must use effective contraction when having sex from the time of the first study drug treatment through a minimum of 4 months after the last study drug treatment. Contraception should be considered for a non-pregnant female partner of childbearing potential.
  • Male and female participants must agree not to donate sperm or eggs, respectively, from the first study drug treatment through 4 months and 7 months after the last study drug treatment, respectively.
  • Female participants may not be breastfeeding at baseline through a minimum of 1 month after the last study drug treatment.
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Glomerular filtration rate (by Cockroft-Gault or equivalent estimation) >= 30 mL/min
  • Serum total bilirubin =< 1.5 X upper limit or normal (ULN) OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for participants with liver metastases
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

  • Has not recovered (recovery is defined as Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 grade =< 1 or return to baseline) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
  • Best response of progressive disease per RECIST 1.1 to first-line platinum doublet chemotherapy (i.e., patient must have had stable disease, partial response or complete response on their first restaging scans after starting first-line chemotherapy).
  • Has received more than 1 line of cytotoxic therapy * Prior immunotherapy and targeted therapies (including rovalpituzumab tesirine) are allowed. * For limited-stage disease that progresses after 12 months from the end of initial cytotoxic treatment, the initial cytotoxic treatment will not be counted towards the maximum of one prior line of cytotoxic treatment. For limited stage disease that progresses within 12 months from the end of initial cytotoxic treatment will count as one prior line of cytotoxic treatment.
  • Prior treatment with a PARP inhibitor (not including iniparib) or temozolomide.
  • Use of antineoplastic therapies within 14 days before study treatment initiation.
  • Use of any other investigational agent within 14 days before study treatment initiation.
  • Received radiation therapy =< 14 days before study treatment initiation (single fraction palliative radiotherapy is allowed without a washout). * Prior thoracic irradiation and prophylactic cranial irradiation are allowed.
  • Major surgery within 14 days before study treatment initiation.
  • Diagnosis of myelodysplastic syndrome (MDS).
  • Gastrointestinal disorder affecting absorption.
  • Current or anticipated use of a prohibited P-gp inhibitor or P-gp inducer or BCRP inhibitors.
  • History of another cancer within 2 years before study treatment initiation, with the exception of fully treated cancers unlikely to affect the assessment of the study treatment safety or efficacy including early stage breast, prostate, nonmelanomatous skin, thyroid, cervix and endometrial cancer.
  • Progressive or symptomatic brain metastases. Brain metastases that have been radiated, and that are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded.
  • Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the investigator.

California

Los Angeles
Translational Research In Oncology - US Inc
Status: ACTIVE
Contact: Jonathan W. Goldman
Phone: 310-825-7174
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Jonathan W. Goldman
Phone: 310-633-8400

PRIMARY OBJECTIVE:

I. Evaluate the efficacy of talazoparib in combination with temozolomide as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of talazoparib plus temozolomide as measured by progression-free survival (PFS), overall survival, duration of response, and time to response.

II. To evaluate the safety, tolerability of talazoparib plus temozolomide.

III. To evaluate the pharmacokinetics of talazoparib when given in combination with temozolomide.

IV. To evaluate patient reported outcomes per the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

EXPLORATORY OBJECTIVE:

I. To identify potential biomarkers associated with response to study drug treatment.

OUTLINE:

Patients receive temozolomide orally (PO) on days 1-5 and talazoparib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
UCLA / Jonsson Comprehensive Cancer Center

Principal Investigator
Jonathan W. Goldman

  • Primary ID TRIO-US L-07
  • Secondary IDs NCI-2018-01409, 18-001387
  • Clinicaltrials.gov ID NCT03672773