Platinum Doublet Chemotherapy and Proton Beam Radiation Therapy in Treating Patients With Stage II-III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Phase II Trial of Standard Platinum Doublet Chemotherapy + Various Proton Beam Therapy (PBT) Doses in Order to Determine the Optimal Dose of PBT for Unresectable Stage 2/3 Non-Small Cell Lung Cancer

This randomized phase II trial studies how well platinum doublet chemotherapy and proton beam radiation therapy work in treating patients with stage II-III non-small cell lung cancer that cannot be removed by surgery (unresectable). Drugs used in chemotherapy, such as carboplatin, paclitaxel, etoposide, cisplatin, and pemetrexed 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. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Giving platinum doublet chemotherapy and proton beam radiation therapy may work better in treating patients with non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Stage III Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Radiation: Proton Beam Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the 1-year progression-free survival rates of 72 gray (Gy) and 60 Gy conventionally fractionated proton beam therapy (PBT) (as part of concurrent combined modality therapy).

SECONDARY OBJECTIVE:

I. To assess the adverse events, survival, quality of life, and patterns of failure (local regional, distant metastatic) associated with two dose levels of conventionally fractionated PBT (as part of concurrent combined modality therapy).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.

All patients undergo computed tomography (CT) throughout the study, magnetic resonance imaging (MRI) or CT, and positron emission tomography (PET)/CT during screening.

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years
• Histological confirmation of non-small cell lung cancer
• Forced expiratory volume in 1 second (FEV1) > 1.0 L

• Unresectable or medically inoperable stage 2-3 non-small cell lung cancer (based on computed tomography/positron emission tomography [CT/PET], magnetic resonance imaging [MRI] or CT of brain, and physical exam);

  • Eligible if recurrence after surgery and now has the equivalent stage 2-3 non-small cell lung cancer (NSCLC) OR had sub totally resected stage 2-3 NSCLC
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• White blood cell (WBC) >= 3.0 x 10^9/L
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Hemoglobin (Hgb) >= 9 g/dl
• Platelets (plts) > 100 x 10^9/L
• Serum creatinine < 1.5 x upper limits of normal (ULN)
• Serum bilirubin < 1.5 x ULN
• Provide informed written consent
• Willing to return to enrolling institution for follow-up for a minimum of 1 year
• Ability to undergo potentially curative chemotherapy plus radiotherapy

Exclusion Criteria:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Weight loss of > 10% in the past 3 months
• Distant metastases (M1 disease)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, lupus, usual interstitial pneumonitis (UIP), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any investigational agent, that would be considered as a treatment for the primary neoplasm
• Active second malignancy
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Received chemotherapy for lung cancer within 6 months of registration
• Previous chest radiotherapy that would overlap with the proton field

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (platinum doublet chemotherapy, lower dose PBT); Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Pemetrexed; Chemotherapy; Other Names: MTA; Multitargeted Antifolate; Pemfexy; Drug: Paclitaxel; Chemotherapy; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Carboplatin; Chemotherapy; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Cisplatin; Chemotherapy; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Etoposide; Chemotherapy; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Radiation: Proton Beam Radiation Therapy; Undergo PBT; Other Names: Proton Radiation Therapy; PBRT; Proton; Proton EBRT; Proton External Beam Radiotherapy; Radiation, Proton Beam
Experimental: Arm C (platinum doublet chemotherapy, higher dose PBT); Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Paclitaxel; Chemotherapy; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Carboplatin; Chemotherapy; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Radiation: Proton Beam Radiation Therapy; Undergo PBT; Other Names: Proton Radiation Therapy; PBRT; Proton; Proton EBRT; Proton External Beam Radiotherapy; Radiation, Proton Beam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Progression Free Survival (PFS)	A Cox proportional hazards model stratified by stratification factors will be used to model PFS as a function of dose to test for an overall dose effect (a one-sided p-value < 0.10 will be considered as significant evidence of a dose effect). Subsequently, separate Cox models stratified by stratification factors will compare PFS between 72 Gy and 60 Gy (for each, a one-sided p-value < 0.10 will be considered as significant evidence of superiority). Kaplan Meier estimates and curves by dose level will also be generated	From randomization to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Will be modeled using Cox models. Kaplan-Meier estimates and curves by dose level will also be generated. OS will again be analyzed as exploratory analysis after 50 deaths per primary pairwise comparison have occurred or after all patients have completed follow-up (whichever occurs first).	From randomization to death due to any cause, assessed up to 5 years
Number of Participants With Adverse Events	Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Adverse events are graded on a scale of 0-5 with 5 being worst. The number of participants with Grade 2 or higher adverse events will be reported.	Up to 5 years
Proportion of Participants With Local-regional Failure	Defined as the proportion of participants with documentation of local recurrence. The cumulative incidence of local failure will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).	Up to 5 years
Proportion of Participants With Distant Metastasis	Defined as the proportion of participants with documentation of distant metastasis. The cumulative incidence of distant metastasis will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).	Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Post Treatment	Measured using the single item Linear Analogue Self-Assessment scale. Descriptive statistics by dose level at each time point will include means, standard deviations, medians, and ranges for each scale. Descriptive graphical techniques will include mean plots by dose over time for each scale. Mixed models will be used to compare each scale across dose levels at each post-baseline time point while adjusting for the baseline value of scale. Will graphically explore patterns of missing data and will employ pattern mixture models for longitudinal analyses. The lowest number measuring worst and higher number measuring best outcome.	Up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Terence T. Sio, M.D., M.S., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2017
• Primary Completion (Actual): December 23, 2023
• Study Completion (Actual): December 23, 2023

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Physical Phenomena; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Elements; Metals; Health Care Economics and Organizations; Metals, Heavy; Ions; Electrolytes; Platinum Compounds; Radiotherapy; Transition Elements; Gases; Elementary Particles; Heavy Ion Radiotherapy; Cations, Monovalent; Cations; Hydrogen; Nucleons; Economics; Pemetrexed; Etoposide; Carboplatin; Paclitaxel; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Proton Therapy; Protons; Taxes
• Other Study ID Numbers: MC1623; NCI-2017-02481 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 16-008343 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No