NCT01993810

Brief Summary

This randomized phase III trial studies proton chemoradiotherapy to see how well it works compared to photon chemoradiotherapy in treating patients with stage II-IIIB non-small cell lung cancer that cannot be removed by surgery. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor, such as photon or proton beam radiation therapy, may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as paclitaxel, carboplatin, etoposide, and cisplatin, 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. It is not yet known whether proton chemoradiotherapy is more effective than photon chemoradiotherapy in treating non-small cell lung cancer.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
330

participants targeted

Target at P50-P75 for phase_3

Timeline
29mo left

Started Feb 2014

Longer than P75 for phase_3

Geographic Reach
1 country

30 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Feb 2014Oct 2028

First Submitted

Initial submission to the registry

November 12, 2013

Completed
13 days until next milestone

First Posted

Study publicly available on registry

November 25, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

February 3, 2014

Completed
13.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

December 18, 2024

Status Verified

December 1, 2024

Enrollment Period

13.8 years

First QC Date

November 12, 2013

Last Update Submit

December 13, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • Overall Survival

    The time from study registration until death or last follow-up

    From registration until death or last follow-up; analysis occurs after 390 deaths have been reported

Secondary Outcomes (2)

  • Progression-free survival

    From registration to date of local failure, regional failure, distant failure, death from any cause, or until last follow-up. Analysis occurs after 390 deaths have been reported.

  • Adverse events

    From start of treatment to end of follow-up

Study Arms (2)

Arm I (photon beam radiation therapy and chemotherapy)

ACTIVE COMPARATOR

Patients undergo photon beam radiation therapy 5 days per week for a total of 35 fractions and receive either paclitaxel\* IV over 1 hour and carboplatin\* IV weekly during radiation therapy or etoposide IV on days 1-5 and 29-33 and cisplatin IV on days 1, 8, 29, and 36. Patients with non-squamous cell cancer may receive pemetrexed IV and carboplatin IV on every 21 days. Patients who receive paclitaxel and carboplatin must complete 2 courses of consolidation therapy. CONSOLIDATION THERAPY: Beginning 3-6 weeks after chemoradiotherapy, patients receive either paclitaxel IV over 3 hours and carboplatin IV on day 1 or durvalumab IV every 2 weeks. Treatment repeats every 21 days for 2 courses or every 2 weeks for up to 12 months for durvalumab in the absence of disease progression or unacceptable toxicity. Patients with non-squamous cell carcinoma may receive durvalumab or pemetrexed IV and carboplatin IV on day 1 every 21 days for up to 4 courses.

Drug: CarboplatinDrug: CisplatinBiological: DurvalumabDrug: EtoposideDrug: PaclitaxelDrug: Pemetrexed DisodiumRadiation: Photon Beam Radiation TherapyOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Arm II (proton beam radiation therapy and chemotherapy)

EXPERIMENTAL

Patients undergo proton beam radiation therapy 5 days per week for a total of 35 fractions and receive either paclitaxel\* and carboplatin\*, etoposide and cisplatin, or pemetrexed and carboplatin (for non-squamous cell cancer patients only) as in Arm I. Patients who receive paclitaxel and carboplatin must complete 2 courses of consolidation therapy. CONSOLIDATION THERAPY: Beginning 3-6 weeks after chemoradiotherapy, patients receive either paclitaxel IV over 3 hours and carboplatin IV on day 1 or durvalumab IV every 2 weeks. Treatment repeats every 21 days for 2 courses or every 2 weeks for up to 12 months for durvalumab in the absence of disease progression or unacceptable toxicity. Patients with non-squamous cell carcinoma may receive durvalumab or pemetrexed IV and carboplatin IV on day 1 every 21 days for up to 4 courses.

Drug: CarboplatinDrug: CisplatinBiological: DurvalumabDrug: EtoposideDrug: PaclitaxelDrug: Pemetrexed DisodiumRadiation: Proton Beam Radiation TherapyOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Interventions

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)
DurvalumabBIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Given IV

Also known as: Alimta, LY231514, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Undergo photon beam radiation therapy

Arm I (photon beam radiation therapy and chemotherapy)

Undergo proton beam radiation therapy

Also known as: PBRT, Proton Radiation Therapy
Arm II (proton beam radiation therapy and chemotherapy)

Ancillary studies

Also known as: Quality of Life Assessment
Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Ancillary studies

Arm I (photon beam radiation therapy and chemotherapy)Arm II (proton beam radiation therapy and chemotherapy)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically proven diagnosis of non-small cell lung cancer
  • Clinical American Joint Committee on Cancer (AJCC) (AJCC, 7th ed.) II, IIIA or IIIB (with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team within 60 days prior to registration; note: for patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and/or a medical oncologist or pulmonologist
  • Patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor are eligible
  • Patients who refuse surgery are eligible
  • Patients who develop local recurrence after surgery and rendered candidate for definitive concurrent chemoradiation are also eligible
  • Patients who have received systemic treatment (up to 4 cycles of induction chemotherapy, or up to 6 months of targeted therapy) are eligible
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
  • History/physical examination within 30 days prior to registration including resting heart rate;
  • Fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scan for staging within 60 days prior to registration
  • Magnetic resonance imaging (MRI) scan with contrast of the brain (preferred) or CT scan of the brain with contrast within 60 days prior to registration;
  • Forced expiratory volume in one second (FEV1) \>= 0.8 liter or \>= 35% predicted with or without bronchodilator within 90 days prior to registration;
  • Patients who meet the criterion above without oxygen (O2), but who need acute (started within 10 days prior to registration) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable
  • Zubrod performance status 0-1 within 30 days prior to registration
  • Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 obtained within 30 days prior to registration
  • Platelets \>= 100,000 cells/mm\^3 obtained within 30 days prior to registration
  • +16 more criteria

You may not qualify if:

  • Prior invasive malignancy unless disease free for a minimum of 3 years; however, skin cancer and in situ carcinomas of the breast, oral cavity, cervix, and other organs and are permissible
  • Patients with prior history of either small cell lung cancer or NSCLC regardless of the treatment received, other than patients who have recurrent disease following resection
  • Prior systemic chemotherapy for the study cancer, if more than 4 cycles of induction chemotherapy or more than 6 months of targeted therapy; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  • Transmural myocardial infarction within the last 6 months;
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness other than the diagnosed lung cancer requiring hospitalization or precluding study therapy within 30 days before registration;
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
  • Unintentional weight loss \> 10% within 30 days prior to registration
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, 32209, United States

Location

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

Location

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Upper Chesapeake Medical Center

Bel Air, Maryland, 21014, United States

Location

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, 21044, United States

Location

Tate Cancer Center

Glen Burnie, Maryland, 21061, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mass General/North Shore Cancer Center

Danvers, Massachusetts, 01923, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

ProCure Proton Therapy Center-Somerset

Somerset, New Jersey, 08873, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Sleepy Hollow

Sleepy Hollow, New York, 10591, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

West Chester Hospital

West Chester, Ohio, 45069, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Cancer Specialists-Dowell Springs

Knoxville, Tennessee, 37909, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson Regional Care Center-Katy

Houston, Texas, 77094, United States

Location

MD Anderson Regional Care Center-Bay Area

Nassau Bay, Texas, 77058, United States

Location

MD Anderson Regional Care Center-Sugar Land

Sugar Land, Texas, 77478, United States

Location

MD Anderson Regional Care Center-The Woodlands

The Woodlands, Texas, 77384, United States

Location

ProCure Proton Therapy Center-Seattle

Seattle, Washington, 98133, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

  • Ramella S, D'Angelillo RM. Proton beam or photon beam radiotherapy in the treatment of non-small-cell lung cancer. Lancet Oncol. 2020 Jul;21(7):873-875. doi: 10.1016/S1470-2045(20)30246-1. No abstract available.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

CarboplatinCisplatin1,2-diaminocyclohexaneplatinum II citratePlatinumdurvalumabImmunoglobulin GDisulfidesEtoposidePaclitaxelTaxesPemetrexedProton TherapyProtons

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsMetals, HeavyElementsTransition ElementsMetalsImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSulfidesAnionsIonsElectrolytesHydrogen SulfideSulfur CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicDiterpenesTerpenesEconomicsHealth Care Economics and OrganizationsGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, DicarboxylicHeavy Ion RadiotherapyRadiotherapyTherapeuticsCations, MonovalentCationsHydrogenGasesNucleonsElementary ParticlesPhysical Phenomena

Study Officials

  • Zhongxing Liao

    NRG Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 12, 2013

First Posted

November 25, 2013

Study Start

February 3, 2014

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

October 1, 2028

Last Updated

December 18, 2024

Record last verified: 2024-12

Locations