Trial record 1 of 1 for:
A082002
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
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| ClinicalTrials.gov Identifier: NCT04929041 |
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Recruitment Status :
Recruiting
First Posted : June 18, 2021
Last Update Posted : May 25, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy [carboplatin, pemetrexed, paclitaxel, nab-paclitaxel]) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) 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. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. 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 | Procedure: Biopsy Procedure: Biospecimen Collection 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 detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 427 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 Genetics related topics:
Lung cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (immunotherapy, +/- chemotherapy)
See Detailed Description
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Procedure: Biopsy
Undergo tissue biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT
Other Names:
Biological: Ipilimumab Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Drug: Nab-paclitaxel Given IV
Other Names:
Biological: Nivolumab Given IV
Other Names:
Drug: Paclitaxel Given IV
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Drug: Pemetrexed Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment |
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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. Patients also undergo MRI or CT on study. Patients may undergo blood sample collection and tissue biopsy on study.
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Procedure: Biopsy
Undergo tissue biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT
Other Names:
Biological: Ipilimumab Given IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Drug: Nab-paclitaxel Given IV
Other Names:
Biological: Nivolumab Given IV
Other Names:
Drug: Paclitaxel Given IV
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Drug: Pemetrexed Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Stereotactic Body Radiation Therapy Undergo SBRT
Other Names:
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Primary Outcome Measures :
- 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 intent-to-treat (ITT) basis.
- Overall survival (OS) (Phase III) [ Time Frame: From randomization and death of all causes, assessed up to 5 years ]Will be performed on an 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 :
- 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).
- 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.
- Quality of life [ Time Frame: Up to 5 years ]
- 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.
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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 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 prior to registration 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 [registered trademark]) 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 106 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Steven E Schild | Alliance for Clinical Trials in Oncology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | May 25, 2023 |
| Last Verified: | April 2023 |
| 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 |
| 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 |