Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Davis
Dates
study started
estimated completion
Principal Investigator
by Megan E. Daly (ucdavis)

Description

Summary

This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (advanced) or has spread to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin, pemetrexed, paclitaxel and nab-paclitaxel, 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. The addition of radiation therapy to usual treatment may stop the cancer from growing and increase the life of patients with advanced non-small cell lung cancer who are PD-L1 negative.

Official Title

A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without SBRT for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer

Details

PRIMARY OBJECTIVE: I. To assess if stereotactic body radiation therapy (SBRT) improves the progression free survival (PFS, phase II portion) and overall survival (OS, phase III portion) of advanced stage non-small cell lung cancer (NSCLC) patients with PD-L1 tumor proportion score (TPS) < 1% who receive immunotherapy with or without chemotherapy. SECONDARY OBJECTIVES: I. To estimate and compare the rates of >= grade 3-4 and all grade adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 between the arms. II. To summarize and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) between the arms. III. To determine and compare the objective response rate (ORR) per RECIST between the arms (including at both irradiated and un-irradiated sites). QUALITY OF LIFE (QOL) OBJECTIVE: I. To assess the health-related QOL in both treatment arms. CORRELATIVE SCIENCE OBJECTIVE: I. To evaluate changes in the peripheral immune microenvironment between the arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive 1 of 6 treatment options. Some patients receive immunotherapy alone whether they have squamous or non-squamous histology. OPTION 1: Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients with non-squamous histology receive 1 of 2 options. OPTION 2: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, carboplatin IV on days 1 and 22 of cycles 1 and 2, and pemetrexed IV over 10 minutes on days 1 and 22 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. OPTION 3: Patients receive nivolumab IV over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV on days 1 and 22 of cycle 1 and pemetrexed IV over 10 minutes on days 1 and 22 of cycle 1. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients with squamous histology receive 1 of 3 options. OPTION 4: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV and paclitaxel IV over 1-96 hours on days 1 and 22 of cycles 1 and 2. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. OPTION 5: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV on days 1 and 22 of cycles 1 and 2, and nab-paclitaxel IV over 30 minutes on days 1, 8, 15, 22, 29 and 36 of cycles 1 and 2. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. OPTION 6: Patients receive nivolumab IV over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on days 1 of each cycle. Patients also receive carboplatin IV and paclitaxel IV over 1-96 hours on days 1 and 22 of cycle 1. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Arm B: Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of SBRT every other day. After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for years 4-5 following randomization until disease progression. Following disease progression patients are followed for survival every 6 months for up to 5 years following randomization.

Keywords

Advanced Lung Adenocarcinoma Advanced Lung Adenosquamous Carcinoma Advanced Lung Non-Small Cell Carcinoma Metastatic Lung Adenocarcinoma Metastatic Lung Adenosquamous Carcinoma Metastatic Lung Non-Small Cell Carcinoma 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 Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Adenocarcinoma Adenocarcinoma of Lung Carcinoma, Adenosquamous Paclitaxel Albumin-Bound Paclitaxel Carboplatin Pembrolizumab Nivolumab Pemetrexed Ipilimumab Nab-paclitaxel Quality-of-Life Assessment Stereotactic Body Radiation Therapy

Eligibility

For people ages 18 years and up

Inclusion Criteria:

  • Histologic or cytologic diagnosis of stage IV NSCLC using version American Joint Committee on Cancer (AJCC) 8th edition (includes M1a, M1b, and M1c stage disease). Patients with Stage IIIB and IIIC disease are eligible if they are not a candidate for combined chemotherapy and radiation
  • PD-L1 expression tumor proportion score (TPS) < 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed patients are not eligible. The assay must have been performed locally by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory. The type of assay will be recorded
  • For non-squamous patients only (adenocarcinoma or adenosquamous): EGFR, ALK and ROS1 testing must be done locally. No patients with known actionable EGFR mutations (except exon 20 insertion), ALK or ROS1 mutations that can be treated with oral tyrosine inhibitors
  • Measurable disease based on RECIST 1.1, including at least two cancerous deposits. At least one deposit must be RECIST measurable (and not to be irradiated) while at least one OTHER deposit (measurable or non-measurable) must meet criteria for stereotactic body radiation therapy (SBRT)
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • No prior systemic chemotherapy or immunotherapy for advanced NSCLC
  • No prior treatment with checkpoint inhibitors for metastatic lung cancer
  • Chemotherapy for non-metastatic disease (e.g., adjuvant therapy) or immunotherapy for locally advanced stage III disease is allowed if terminated at least 6 months prior to registration
  • No systemic immunostimulatory or immunosuppressive drugs, including > 10 mg prednisone equivalent per day, within 2 weeks or 5 half-live of the drug, whichever is shorter
  • >= 1 week since palliative (including central nervous system [CNS]) radiotherapy to any tumor site
  • No prior allogeneic tissue/solid organ transplant
  • No uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
  • No current pneumonitis or history of non-infectious pneumonitis that required steroids
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration
  • No active auto-immune disease that requires systemic therapy within 2 years prior to registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  • No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
  • No patients with symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with small asymptomatic brain metastases are eligible as are patients with treated brain metastases that require no steroids
  • Not pregnant and not nursing, because this study involves radiation as well as potentially chemotherapy which have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
  • No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 2 years. Participants with non-melanoma skin cancers or carcinoma in-situ (e.g., breast carcinoma, urothelial carcinoma or cervical cancer in situ) or localized prostate cancer (T1-3, N0, M0) that have undergone potentially curative therapy are eligible
  • No hypersensitivity (>= grade 3) to immunotherapy and/or any of its excipients
  • No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,FluMist) are live attenuated vaccines and are not allowed. COVID-19 vaccine is allowed
  • Absolute neutrophil count (ANC) >= 1,500/mm3

  • Platelet count >= 100,000/mm3

  • Calculated (Calc.) creatinine clearance >= 45 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • Alta Bates Summit Medical Center-Herrick Campus accepting new patients
    Berkeley California 94704 United States

Lead Scientist at UC Cancer

  • Megan E. Daly (ucdavis)
    Associate Professor, Radiation Oncology. Authored (or co-authored) 107 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Cancer Institute (NCI)
ID
NCT04929041
Phase
Phase 2/3 research study
Study Type
Interventional
Participants
Expecting 100 study participants
Last Updated