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

NCT03830918 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 18-001791NCI-2018-02806
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the best dose of temozolomide and how well it works with niraparib and atezolizumab in treating patients with solid tumors that have spread to other places in the body (advanced) and extensive-stage small cell lung cancer with a complete or partial response to platinum-based first-line chemotherapy. 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. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving temozolomide, niraparib and atezolizumab may work better in treating patients with advanced solid tumors and extensive-stage small cell lung cancer.

Conditions

Advanced Malignant Solid Neoplasm; 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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose of niraparib and temozolomide combination (Phase Ib)

  At 28 days

• Progression-free survival (Phase II)

  Assessed per Response Evaluation Criteria in Solid Tumors 1.1. 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.

  From randomization to cancer progression, assessed up to 36 months

Secondary Outcomes (3)

• Objective response rate

  Up to 36 months

• Overall survival

  From randomization to death by any cause, assessed up to 36 months

• Incidence of adverse events per Common Terminology Criteria for Adverse Events version 4.0

  Up to 36 months

Other Outcomes (1)

• Quality of life per Functional Assessment of Cancer Therapy - Lung questionnaire (FACT-L)

  Up to 36 months

Study Arms (2)

Arm A (temozolomide, niraparib, atezolizumab)

EXPERIMENTAL

Patients receive temozolomide PO QD on days 1-5 and niraparib PO QD on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care atezolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Atezolizumab; Drug: Niraparib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Temozolomide

Arm B (atezolizumab)

ACTIVE COMPARATOR

Patients receive standard of care atezolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Atezolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Arm A (temozolomide, niraparib, atezolizumab); Arm B (atezolizumab)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Arm A (temozolomide, niraparib, atezolizumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (temozolomide, niraparib, atezolizumab); Arm B (atezolizumab)

Questionnaire Administration OTHER

Ancillary studies

Arm A (temozolomide, niraparib, atezolizumab); Arm B (atezolizumab)

Temozolomide DRUG

Given PO

Also known as: 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, TMZ

Arm A (temozolomide, niraparib, atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent.
• Cytologically or histologically confirmed advanced and incurable solid malignancy.
• For the Phase 1b, Part 2 cohort, participants must have a tumor type for which atezolizumab is an Food and Drug Administration (FDA) approved therapy.
• 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.

You may not qualify if:

• 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.
• Use of antineoplastic therapies within 21 days before day 1 of study treatment. (Atezolizumab does not require a washout.) Use of prophylactic cranial irradiation or thoracic irradiation within 14 days before day 1 of study treatment. Palliative radiation to bone lesions must be completed at least 7 days before day 1 of study treatment.
• Use of any other investigational agent within 21 days before day 1 of study treatment.
• 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 day 1 of study treatment.
• Requirement for IV alimentation (at the time of day 1 of study treatment).
• Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• History of another cancer within 3 years before day 1 of study treatment, 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 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.
• For both arms in phase 2, participants should already be receiving atezolizumab infusions and will continue to do so while on trial. There should be no contra-indication to a PD-1 or PD-L1 inhibitor in the opinion of the treating investigator. This includes active autoimmune disease or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication, above a dose equivalent to 10 mg prednisone. Exceptions include participants with vitiligo, resolved childhood asthma/atopy, participants who require intermittent use of bronchodilators or local steroid injections, and participants with a history of hypothyroidism or adrenal insufficiency taking a stable dose of replacement therapy.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Translational Research in Oncology-U.S: collaborator
• Tesaro, Inc.: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Small Cell Lung Carcinoma

Interventions

atezolizumab; niraparib; Temozolomide

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jonathan W Goldman

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 5, 2019
• Study Start: March 6, 2019
• Primary Completion (Estimated): January 3, 2027
• Study Completion (Estimated): January 3, 2027
• Last Updated: February 12, 2026

Record last verified: 2025-11

Locations

US (1)