Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Adenocarcinoma

Adenocarcinoma of Lung

Carcinoma, Adenosquamous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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 or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

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, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

Biopsy

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Positron Emission Tomography

Quality-of-Life Assessment

Stereotactic Body Radiation Therapy

Site Public Contact

Uma Suryadevara

Arya Amini

Megan E. Daly

Alison K. Conlin

Steven R. Schuster

Gregory A. Masters

Irina G. Veytsman

Raphael L. Yechieli

Joshua T. Mckenzie

Young Kwang Chae

Frank Weinberg

Christine M. Bestvina

Sinisa Stanic

Bryan A. Faller

James A. Wallace

Joseph J. Merchant

Richard L. Deming

Shahzad Siddique

John L. Villano

Matthew D. Cheney

Christopher M. Reynolds

Kathleen J. Yost

Daniel M. Anderson

Jay W. Carlson

A. G. Wernicke

Michael D. Mix

Christine M Bestvina

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 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 may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. 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.

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 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 or patients may receive standard of care systemic immunotherapy. Patients also undergo magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as echocardiography (ECHO) during screening.

Arm B: Patients receive nivolumab 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 or patients may receive standard of care systemic immunotherapy. Patients also undergo 3 fractions of SBRT every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

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.

Testing the Addition of Radiation Therapy to Immunotherapy for Stage IV Non-Small Cell Lung Cancer Patients Who Are PD-L1 Negative

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

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.

Will be performed on an intent-to-treat (ITT) basis.

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.

Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).

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.

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.

National Cancer Institute (NCI)

Heart and Blood Diseases

Pleural Effusion, Malignant

Pleural Effusion

Pericardial Effusion

Adenocarcinoma, Bronchiolo-Alveolar

Pleural Diseases

Pleural Neoplasms

Heart Diseases

Amino Acids

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive erlotinib hydrochloride PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.

Erlotinib

Pasi A Janne

This randomized phase II trial studies how well erlotinib hydrochloride with or without carboplatin and paclitaxel works in treating patients with stage III-IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and 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. Giving erlotinib hydrochloride together with carboplatin and paclitaxel may kill more tumor cells than giving either drug alone.

PRIMARY OBJECTIVES:

I. To determine the distribution of progression-free survival (PFS) in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) (erlotinib hydrochloride) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

SECONDARY OBJECTIVES:

I. To determine the radiographic response rate in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

II. To determine the frequency of epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations and anaplastic lymphoma kinase (ALK) translocations in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers.

III. To determine the response rate and time to progression in patients with and without EGFR mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

IV. To determine the response rate and time to progression in patients with and without K-ras mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

V. To determine the median and overall survival of patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

VI. To estimate the response rate, progression-free, and overall survival of patients with echinoderm microtubule associated protein like (EML)4-ALK translocation who received OSI-774 erlotinib alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib hydrochloride as in Arm I. Patients also receive paclitaxel intravenously (IV) over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.

After completion of study treatment, patients are followed at least every 3 months for 1 year and then every 6 months for up to 2 years.

Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

A Phase II Randomized Study of OSI-774 (Erlotinib) (NSC #718781) With or Without Carboplatin/Paclitaxel in Patients With Previously Untreated Adenocarcinoma of the Lung Who Never Smoked or Were Former Light Smokers

Overall survival (OS) is defined as the time from patient randomization (arm assignment) to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.

EGFR mutations were performed at the Dana-Farber Cancer Institute using a sensitive heteroduplex method coupled with enzymatic digestion as previously reported (Janne PA, et al: A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 12:751-758, 2006). All positive findings were independently verified and subjected to sequencing. The mutation analyses were blinded to the participants' clinical outcome.

Response and EGFR mutation status are defined in previous outcome measures.

Progression free survival is defined in previous outcome measures. GIven the small number of KRAS mutant participants, the analysis combines data from both arms.

Overall response is defined in previous outcome measures. GIven the small number of KRAS mutant participants in each treatment arm, the analysis combines data from both arms.

The product limit estimator developed by Kaplan Meier will be used to graphically describe progression free survival for patients randomized to each study arm.

The 18 week progression-free survival rate was defined as the proportion of patients that were alive progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.

The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:

Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions

The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.

Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

Patients receive oral erlotinib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm A: Erlotinib

Patients receive erlotinib as in arm I. Patients also receive paclitaxel IV over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of treatment, patients may continue to receive erlotinib alone as above.

Arm B: Erlotinib/Carboplatin/Paclitaxel

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

0 - fully active

1 - minimal symptoms

Classifies patients according to their functional impairment. Scores range from 0 (fully active) to 5 (death).

ECOG Performance Status

Never smoker

Light former smoker

Smoking history

Bronhioloalveolar cancer

Adenocarcinoma with bronchioloalveolar features

Histology

Pasi Janne, MD, PhD

18 Weeks Progression Free Survival (PFS) Rate

Overall Response Rate

Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.

Overall Survival

EGFR Mutant

EGFR Wild Type

EGFR mutation analysis was successfully performed in 164 participants; 17 participants had insufficient material or DNA for analysis.

Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status

Overall Response Rate by EGFR Mutation Status

Mutant

Wild Type

Progression Free Survival With KRAS Mutation Status

Overall Response Rate With KRAS Mutational Status

Overall Study

Carcinoma, Squamous Cell

Carcinoma, Large Cell

Dermatologic Agents

Docetaxel

Bevacizumab

Etoposide

Cisplatin

Lenograstim

Etoposide phosphate

Podophyllotoxin

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Adjuvants, Immunologic

Keratolytic Agents

Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.

Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.

Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.

Filgrastim

Pegfilgrastim

Radiation Therapy

Antoinette J Wozniak

This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin, etoposide, and docetaxel, work in different ways to stop the growth of \[cancer/tumor\] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with radiation therapy and bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the frequency and severity of toxic effects of induction therapy comprising cisplatin, etoposide, and radiotherapy with or without bevacizumab followed by consolidation therapy comprising docetaxel and bevacizumab, in terms of grade 4 or 5 hemorrhage, in patients with newly diagnosed, unresectable, stage III non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. Determine progression-free and overall survival of patients treated with these regimens.

II. Determine response (confirmed, unconfirmed, partial, and complete) in patients with measurable disease treated with these regimens.

OUTLINE: This is a pilot, multicenter study. Patients are stratified according to risk (high\* vs low).

NOTE: \*High-risk stratum closed to accrual as of 2/20/09.

INDUCTION THERAPY: Patients in each stratum are assigned to 1 of 3 sequential treatment groups.

GROUP 1: Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.

GROUP 2: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.

GROUP 3: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.

CONSOLIDATION CHEMOTHERAPY: Beginning 3-6 weeks after completion of induction therapy, all patients receive consolidation chemotherapy comprising docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing until blood counts recover OR pegfilgrastim SC once on day 2.

Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 4 years.

Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-small Cell Lung Cancer

Only adverse events that are possibly, probably or definitely related to study drug are reported.

From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions.

All eligible patients, both low-risk and high-risk strata combined, who received concurrent chemotherapy and radiotherapy.

Concurrent Chemotherapy and Radiotherapy

All eligible patients, both low-risk and high-risk strata combined, who received consolidation therapy with Docetaxel and Bevacizumab.

Consolidation Therapy With Docetaxel and Bevacizumab

Low Risk Patient Stratum

High Risk Patient Stratum

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All eligible patients who received protocol treatment.

Lung Committee Statistician

Acidosis (metabolic or respiratory)

Arthritis (non-septic)

Calcium, serum-low (hypocalcemia)

Carbon monoxide diffusion capacity (DL(co))

Creatinine

Dehydration

Dyspnea (shortness of breath)

Esophagitis

FEV(1)

Febrile neutropenia

All eligible patients, both low-risk and high-risk strata combined, who received protocol therapy.

Adverse Events

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Addition of Radiation Therapy to Immunotherapy for Stage IV Non-Small Cell Lung Cancer Patients Who Are PD-L1 Negative	NCT04929041	Lung Adenocarci... Lung Adenosquam... Lung Non-Small ... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C...	Biopsy Biospecimen Col... Computed Tomogr... Echocardiograph... Ipilimumab Magnetic Resona... Nivolumab Positron Emissi... Quality-of-Life... Stereotactic Bo...	18 Years -	National Cancer Institute (NCI)
Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer	NCT00126581	Lung Adenocarci... Lung Adenosquam... Malignant Peric... Malignant Pleur... Minimally Invas... Stage IIIB Lung... Stage IV Lung N...	Carboplatin Erlotinib Erlotinib Hydro... Paclitaxel	18 Years -	National Cancer Institute (NCI)
Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery	NCT00334815	Lung Adenocarci... Lung Adenosquam... Lung Large Cell... Lung Squamous C... Minimally Invas... Stage IIIA Lung... Stage IIIB Lung...	Bevacizumab Cisplatin Docetaxel Etoposide Filgrastim Pegfilgrastim Radiation Thera...	18 Years -	National Cancer Institute (NCI)
Testing the Addition of Radiation Therapy to Immunotherapy for Stage IV Non-Small Cell Lung Cancer Patients Who Are PD-L1 Negative	NCT04929041	Lung Adenocarci... Lung Adenosquam... Lung Non-Small ... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C...	Biopsy Biospecimen Col... Computed Tomogr... Echocardiograph... Ipilimumab Magnetic Resona... Nivolumab Positron Emissi... Quality-of-Life... Stereotactic Bo...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for lung adenosquamous carcinoma