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

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Translational Research in Oncology; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Jonsson Comprehensive Cancer Center

Study Description

Brief Summary:

This phase II trial studies how effective talazoparib and temozolomide are for treating participants with extensive-stage small cell lung cancer that has come back 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 participants with extensive-stage small cell lung cancer than either one alone.

Condition or disease	Intervention/treatment	Phase
Recurrent Extensive Stage Small Cell Lung Carcinoma; Refractory Extensive Stage Small Cell Lung Carcinoma	Drug: Talazoparib; Drug: Temozolomide	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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 OBJECTIVES:

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

OUTLINE:

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

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

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	28 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2 Study of Continuous Talazoparib Plus Intermittent Low-Dose Temozolomide in Patients With Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer (TRIO-US L-07)
Actual Study Start Date :	October 31, 2018
Estimated Primary Completion Date :	November 1, 2019
Estimated Study Completion Date :	November 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (temozolomide, talazoparib); Participants receive temozolomide PO on days 1-5 and talazoparib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Talazoparib; Given PO; Other Names: BMN 673; BMN-673; Drug: Temozolomide; Given PO; Other Names: CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Methazolastone; RP-46161; SCH 52365; Temcad; Temodal; Temodar; Temomedac

Outcome Measures

Primary Outcome Measures :

1. Objective response rate defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIS)T 1.1 [ Time Frame: Up to 1 year ]
   Will be provided along with the corresponding exact 2-sided 95% confidence interval calculated using a method based on the F distribution.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) assessed by RECIST 1.1 [ Time Frame: From treatment initiation to time of first documentation of objective tumor progression or death on study due to any cause, whichever occurs first, assessed up to 1 year ]
   Will be summarized for the safety analysis (SA) set. Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
2. PFS assessed by RECIST 1.1 [ Time Frame: From treatment initiation to time of first documentation of objective tumor progression or death on study due to any cause, whichever occurs first, assessed up to 1 year ]
   Will be summarized for the SA set. Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate. Median event times and 2-sided 95% confidence interval for each median will be provided.
3. Overall survival [ Time Frame: From treatment initiation to death by any cause, assessed up to 1 year ]
   Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
4. Duration of response (CR or PR) per RECIST 1.1 [ Time Frame: From the first documentation of objective tumor response, assessed up to 1 year ]
   Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
5. Time to response (CR or PR) per RECIST 1.1 [ Time Frame: From treatment initiation to the first documentation of objective tumor response, assessed up to 1 year ]
   Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
6. Pharmacokinetics of talazoparib - steady state trough plasma concentrations [ Time Frame: Up to 1 year ]
   To evaluate the pharmacokinetics (steady state trough plasma concentrations) of talazoparib when given in combination with temozolomide

Eligibility Criteria

Layout table for eligibility information

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

Criteria

Inclusion Criteria:

• Able to provide informed consent.
• Cytologically or histologically confirmed small cell lung cancer (SCLC) with extensive-stage disease.
• Relapsed (progressed within 6 months) or refractory (progressed during or within 4 weeks of completing 1st line platinum based regimen).
• Measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Archival or fresh tissue biopsy available for exploratory analyses.
• 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 45 days after the last study drug treatment.
• Male participants must use a condom when having sex from the time of the first study drug treatment through 105 days 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 105 days and 45 days after the last study drug treatment, respectively.
• Female participants may not be breastfeeding at baseline through 45 days after the last study drug treatment.
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Glomerular filtration rate (by Cockroft-Gault or equivalent estimation) >= 30 mL/min
• 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
• Serum total bilirubin =< 1.5 X upper limit or normal (ULN) OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ULN
• 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)4 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.

• Has received more than 1 line of cytotoxic therapy

  • Prior immunotherapy and targeted therapies (including rovalpituzumab tesirine) are allowed.
• 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 within 14 day 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.
• 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.

Contacts and Locations

Locations

Layout table for location information

United States, California
UCLA / Jonsson Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90095
Contact: Jonathan W. Goldman 310-633-8400 jwgoldman@mednet.ucla.edu
Principal Investigator: Jonathan W. Goldman

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center

Translational Research in Oncology

National Cancer Institute (NCI)

Investigators

Layout table for investigator information

Principal Investigator:	Jonathan Goldman	UCLA / Jonsson Comprehensive Cancer Center

More Information

Layout table for additonal information

Responsible Party:	Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT03672773 History of Changes
Other Study ID Numbers:	18-001387; NCI-2018-01409 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); TRIO-US L-07 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center ); P30CA016042 ( U.S. NIH Grant/Contract )
First Posted:	September 14, 2018
Last Update Posted:	February 27, 2019
Last Verified:	October 2018

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No
Product Manufactured in and Exported from the U.S.:		Yes

Keywords provided by Jonsson Comprehensive Cancer Center:

Small Cell Lung Cancer; PARP Inhibitor

Additional relevant MeSH terms:

Layout table for MeSH terms

Carcinoma; Lung Neoplasms; Small Cell Lung Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases	Carcinoma, Bronchogenic; Bronchial Neoplasms; Temozolomide; Talazoparib; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors