Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03672773
Previous Study | Return to List | Next Study

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03672773
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : November 19, 2020
Sponsor:
Collaborators:
Translational Research in Oncology
Pfizer
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 14, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date November 19, 2020
Actual Study Start Date  ICMJE October 31, 2018
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Talazoparib and Low-Dose Temozolomide in Treating Participants With Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer
Official Title  ICMJE 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)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Extensive Stage Small Cell Lung Carcinoma
  • Refractory Extensive Stage Small Cell Lung Carcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Talazoparib
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2018)
28
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2022
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: TRIO-US IST Team 888-798-0719 ISTTeam@mednet.ucla.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03672773
Other Study ID Numbers  ICMJE 18-001387
NCI-2018-01409 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
TRIO-US L-07 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE
  • Translational Research in Oncology
  • Pfizer
Investigators  ICMJE
Principal Investigator: Jonathan Goldman, MD UCLA / Jonsson Comprehensive Cancer Center
PRS Account Jonsson Comprehensive Cancer Center
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP