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Trial record 1 of 1 for:    a082002
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Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Stage IV Non-Small Cell Lung Cancer Patients Who Are PD-L1 Negative

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: NCT04929041
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : November 29, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: Carboplatin Procedure: Computed Tomography Biological: Ipilimumab Procedure: Magnetic Resonance Imaging Drug: Nab-paclitaxel Biological: Nivolumab Drug: Paclitaxel Biological: Pembrolizumab Drug: Pemetrexed Other: Quality-of-Life Assessment Radiation: Stereotactic Body Radiation Therapy Phase 2 Phase 3

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 21, 2021
Estimated Primary Completion Date : December 31, 2027
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm A (immunotherapy, +/- chemotherapy)
See Detailed Description
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Computed Tomography
Undergo CT
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • Paclitaxel Albumin
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Drug: Pemetrexed
Given IV
Other Names:
  • MTA
  • Multitargeted Antifolate
  • Pemfexy

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

Experimental: Arm B ( immunotherapy, +/- chemotherapy, SBRT)
Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of SBRT every other day.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Computed Tomography
Undergo CT
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • Paclitaxel Albumin
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Drug: Pemetrexed
Given IV
Other Names:
  • MTA
  • Multitargeted Antifolate
  • Pemfexy

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

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy




Primary Outcome Measures :
  1. Progression-free survival (PFS) (Phase II) [ Time Frame: From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years ]
    Will be performed on an ITT basis.

  2. Overall survival (OS) (Phase III) [ Time Frame: From randomization and death of all causes, assessed up to 5 years ]
    Will be performed on an intent-to-treat (ITT) basis. The comparison of the distributions of OS between treatment arms will be done with a one-sided stratified log-rank test). The rates at various time points (e.g., every 6 months after randomization) and medians of OS for each arm will be estimated using the Kaplan-Meier estimator. The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios will be estimated using a stratified Cox regression model. The final phase III analysis of OS will be considered as "positive" if the stratified log-rank test statistics Z-value greater than the critical value adjusted for type 1 error using group sequential methods. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic therapy, histology and performance status.


Secondary Outcome Measures :
  1. PFS [ Time Frame: From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years ]
    Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).

  2. Objective response rate (ORR) [ Time Frame: Up to 5 years ]
    Assessed per RECIST for both irradiated and un-irradiated areas. The ORRs between treatments will be compared with Fisher's exact test. The difference of ORR between treatments will be estimated by the Miettinen-Nurminen method and its 95%CI will be given. Multivariable logistic regression will be used to evaluate the treatment effect on ORR while adjusting for significant baseline covariates.

  3. Quality of life [ Time Frame: Up to 5 years ]
  4. Incidence of treatment-related adverse events [ Time Frame: Up to 5 years ]
    Treatment-related toxicity will be summarized by grade, type, and system organ class. Comparisons of the percentages of patients experiencing an adverse event between Arm A and Arm B will be performed using Fisher's exact test.



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:

  • 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/mm^3
  • Platelet count >= 100,000/mm^3
  • 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)

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): NCT04929041


Locations
Show Show 81 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Steven E Schild Alliance for Clinical Trials in Oncology
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04929041    
Other Study ID Numbers: NCI-2021-06042
NCI-2021-06042 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
A082002 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A082002 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma of Lung
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Complex and Mixed
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Nivolumab
Pemetrexed
Ipilimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action