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Niraparib and Temozolomide in Treating Patients With Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy

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ClinicalTrials.gov Identifier: NCT03830918
Recruitment Status : Recruiting
First Posted : February 5, 2019
Last Update Posted : April 23, 2019
Sponsor:
Collaborators:
Translational Research in Oncology
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief Summary:
This phase Ib/II trial studies how well niraparib and temozolomide work in treating patients with extensive-stage small cell lung cancer with a complete or partial response to platinum-based first-line chemotherapy. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in 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 niraparib and temozolomide may work better in treating patients with extensive-stage small cell lung cancer.

Condition or disease Intervention/treatment Phase
Extensive Stage Lung Small Cell Carcinoma Stage III Lung Cancer AJCC v8 Stage IIIA Lung Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Stage IIIC Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Drug: Niraparib Other: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Supportive Care Drug: Temozolomide Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the recommended phase II dose (RP2D) of temozolomide in combination with niraparib. (Phase Ib) II. Evaluate the efficacy of niraparib plus temozolomide (Arm A) compared with best supportive care (Arm B) as measured by progression-free survival (PFS). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of niraparib plus temozolomide compared with best supportive care as measured by overall survival (OS).

II. To evaluate the safety of niraparib plus temozolomide compared with best supportive care as measured by adverse events (AEs).

EXPLORATORY OBJECTIVES:

I. To assess patient-reported outcomes on health-related quality of life and adverse events.

OUTLINE: This is a dose-escalation study of temozolomide. Patients are randomized to 1 of 2 arms.

ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5 and niraparib PO QD on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive best supportive care.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 24 weeks, and then every 12 weeks for up to 1 year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Randomized, Open-Label Study of Niraparib Plus Temozolomide Versus Best Supportive Care as Maintenance Therapy in Patients With Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy (TRIO-US L-06)
Actual Study Start Date : March 6, 2019
Estimated Primary Completion Date : January 3, 2020
Estimated Study Completion Date : January 3, 2021


Arm Intervention/treatment
Experimental: Arm A (temozolomide, niraparib)
Patients receive temozolomide PO QD on days 1-5 and niraparib PO QD on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Niraparib
Given PO
Other Names:
  • MK-4827
  • MK4827

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

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

Active Comparator: Arm B (best supportive care)
Patients receive best supportive care.
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Supportive Care
Receive best supportive care (surveillance)
Other Names:
  • Supportive Therapy
  • Symptom Management
  • Therapy, Supportive




Primary Outcome Measures :
  1. Recommended phase II dose of niraparib and temozolomide combination (Phase Ib) [ Time Frame: At 28 days ]
  2. Progression-free survival per Response Evaluation Criteria in Solid Tumors 1.1 (Phase II) [ Time Frame: From randomization to cancer progression, assessed up to 36 months ]
    A Cox proportional hazards model will be used to estimate the hazard ratio and its 95% confidence interval. A one-sided stratified log-rank tests will be used to compare Arm A versus Arm B.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From randomization to death by any cause, assessed up to 36 months ]
    A one-sided stratified log-rank tests will compare Arm A versus Arm B.

  2. Incidence of adverse events per Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 36 months ]
    Incidence of adverse events (AEs) occurring during the study will be summarized by system organ class and preferred term. Adverse events will also be summarized by causality and grade. Serious adverse events will be listed separately. Descriptive summary statistics will be used to summarize changes over time in laboratory values, vital signs, physical examination findings, and Eastern Cooperative Oncology Group (ECOG) performance status, for all treated participants.


Other Outcome Measures:
  1. Quality of life per Functional Assessment of Cancer Therapy - Lung questionnaire [ Time Frame: Up to 36 months ]
    Will be analyzed by the clinical biostatisticians in the UCLA Department of Medicine Medical Statistics Core.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Willing and able to provide informed consent.
  • Cytologically or histologically confirmed advanced and incurable solid malignancy. For the randomized phase 2 portion of the trial, cytologically or histologically confirmed small cell lung carcinoma (SCLC) with extensive-stage disease is required.
  • For the phase 2 portion of the trial, complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) following 4 to 6 cycles of platinum-based chemotherapy.

    • Thoracic irradiation received as part of the treatment regimen and prophylactic cranial irradiation with a washout period of 14 days are allowed. Participants with limited stage disease receiving thoracic irradiation are excluded.
  • For the phase 2 portion of the trial, able to proceed to randomization within 7 weeks after day 1 of the last cycle of prior chemotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1.
  • Able to swallow the study drugs, has no known intolerance of study drugs or excipients, and able to comply with study requirements.
  • 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 4 weeks of first dose).
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 30 mL/min for participants with creatinine levels > 1.5 X institutional ULN. (Glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]).

    • Creatinine clearance should be calculated using the standard Cockcroft and Gault equation.
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< 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.
  • Albumin >= 2.2 mg/dL.
  • International Normalized Ratio (INR) or Prothrombin Time (PT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy, and then only 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, and then only as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the participant to be eligible, and if assigned to Arm A (niraparib plus temozolomide) the participant must agree to use a highly-effective birth control method from the time of the first study drug treatment through 180 days after the last study drug treatment, or be of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):

    • >= 45 years of age and has not had menses for > 1 year
    • Participants who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
    • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
  • Male participants assigned to Arm A must use a condom when having sex with a pregnant woman and when having sex with a woman of childbearing potential from the time of the first study-drug treatment through 180 days after the last study drug treatment. Contraception should be considered for a non-pregnant female partner of childbearing potential.
  • Male and female participants assigned to Arm A must agree not to donate sperm or eggs, respectively, from the first study-drug treatment through 180 days after the last study drug treatment.
  • Female participants must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
  • Participants must agree to not donate blood during the study or for 90 days after the last dose of study treatment.

Exclusion Criteria:

  • Has not recovered [recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, grade =< 1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
  • Prior treatment with a poly [ADP-ribose] polymerase (PARP) inhibitor (not including iniparib).
  • Use of antineoplastic therapies within 21 days before randomization. Use of prophylactic cranial irradiation or thoracic irradiation within 14 days before randomization. Palliative radiation to bone lesions must be completed 7 days before randomization.
  • Use of any other investigational agent within 21 days before randomization.
  • Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded.
  • Serious accompanying disorder or impaired organ function, including the following:

    • Cardiac (within 3 months before randomization): any unstable ischemic disease, heart failure, or untreated arrhythmia.
    • Major surgery within 3 weeks before randomization.
  • Requirement for IV alimentation (at the time of randomization).
  • Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  • History of another cancer within 3 years before randomization, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded.
  • Gastrointestinal disorder affecting absorption.
  • Participants must not have had radiotherapy encompassing > 20% of the bone marrow within 2 weeks of the first dose or any radiation therapy within 1 week prior to day 1 of protocol therapy.
  • Participants must not have a known hypersensitivity to the components of niraparib or the excipients.
  • Participants must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  • Participants must not have received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
  • Participants must not be pregnant.
  • Participants must not have progressed following first-line chemotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03830918


Contacts
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Contact: Lia Etheridge 1 310-825-7174 LEtheridge@mednet.ucla.edu

Locations
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United States, California
UCLA / Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Contact: Jonathan W. Goldman    310-633-8400    jwgoldman@mednent.ucla.edu   
Contact: Lia Etheridge    310-825-7174    LEtheridge@mednet.ucla.edu   
Principal Investigator: Jonathan W. Goldman         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Translational Research in Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jonathan Goldman UCLA / Jonsson Comprehensive Cancer Center

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Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03830918     History of Changes
Other Study ID Numbers: 18-001791
NCI-2018-02806 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
18-001791 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: February 5, 2019    Key Record Dates
Last Update Posted: April 23, 2019
Last Verified: December 2018

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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
SCLC
PARP Inhibitor
Maintenance Therapy

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