Clinical Trials /

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

NCT03830918

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 18-001791
  • SECONDARY ID: NCI-2018-02806
  • SECONDARY ID: 18-001791
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03830918

Conditions

  • 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

Interventions

DrugSynonymsArms
NiraparibMK-4827, MK4827Arm A (temozolomide, niraparib)
TemozolomideCCRG-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, TemomedacArm A (temozolomide, niraparib)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (temozolomide, niraparib)ExperimentalPatients 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.
  • Niraparib
  • Temozolomide
Arm B (best supportive care)Active ComparatorPatients receive best supportive care.

    Eligibility 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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Recommended phase II dose of niraparib and temozolomide combination (Phase Ib)
    Time Frame:At 28 days
    Safety Issue:
    Description: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

    Measure:Overall survival
    Time Frame:From randomization to death by any cause, assessed up to 36 months
    Safety Issue:
    Description:A one-sided stratified log-rank tests will compare Arm A versus Arm B.
    Measure:Incidence of adverse events per Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 36 months
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Jonsson Comprehensive Cancer Center

    Trial Keywords

    • Small Cell Lung Cancer
    • SCLC
    • PARP Inhibitor
    • Maintenance Therapy

    Last Updated