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Comparing Photon Therapy To Proton Therapy To Treat Patients With Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01993810
First received: November 12, 2013
Last updated: June 10, 2016
Last verified: June 2016
  Purpose
This randomized phase III trial studies proton chemoradiotherapy to see how well it works compared to photon chemoradiotherapy in treating patients with stage II-III 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 or by stopping them from dividing. It is not yet known whether proton chemoradiotherapy is more effective than photon chemoradiotherapy in treating non-small cell lung cancer.

Condition Intervention Phase
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Radiation: photon beam radiation therapy
Radiation: proton beam radiation therapy
Drug: paclitaxel
Drug: carboplatin
Drug: etoposide
Drug: cisplatin
Procedure: quality-of-life assessment
Other: questionnaire administration
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial Comparing Overall Survival After Photon Versus Proton Chemoradiotherapy for Inoperable Stage II-IIIB NSCLC

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From registration until death or last follow-up; analysis occurs after 390 deaths have been reported, predicted to occur at 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 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, predicted to occur at 7 years ] [ Designated as safety issue: No ]
    The time from study registration until the first occurrence of local, regional, or distant progression, or death from any cause, or until last follow-up. Analysis occurs after 390 deaths have been reported, predicted to occur at 7 years.

  • Adverse events [ Time Frame: From start of treatment to at least 12 months following completion of chemoradiation ] [ Designated as safety issue: Yes ]
    Incidence of treatment-related grade 3-5 adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.

  • Quality of life (QOL) [ Time Frame: From registration until 12 months following completion of chemoradiation ] [ Designated as safety issue: No ]
    Change in symptom burden and QOL as measured by the single esophagitis and shortness of breath items and the entire lung cancer module of the MDASI-Lung, SOBQ, and EuroQol-5 dimension (EQ-5D)-derived health utility score.

  • Cost-effectiveness [ Time Frame: From registration until 12 months following completion of chemoradiation ] [ Designated as safety issue: No ]
    Cost-effectiveness expressed in dollars per quality-adjusted life year (QALY).

  • Changes in pulmonary function [ Time Frame: From registration until 12 months following completion of chemoradiation ] [ Designated as safety issue: No ]
    Change since baseline in pulmonary function test results.


Estimated Enrollment: 560
Study Start Date: February 2014
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (photon beam radiation therapy and chemotherapy)

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.

*In both arms, patients who receive paclitaxel and carboplatin must complete consolidation therapy.

CONSOLIDATION THERAPY: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Radiation: photon beam radiation therapy
Undergo photon beam radiation therapy
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Experimental: Arm II (proton beam radiation therapy and chemotherapy)

Patients undergo proton beam radiation therapy 5 days per week for a total of 35 fractions and receive either paclitaxel* and carboplatin* or etoposide and cisplatin as in Arm I.

*In both arms, patients who receive paclitaxel and carboplatin must complete consolidation therapy.

CONSOLIDATION THERAPY: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Radiation: proton beam radiation therapy
Undergo proton beam radiation therapy
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) in patients with stage II-IIIB non-small cell lung cancer (NSCLC) after image guided, motion-managed photon radiotherapy (Arm 1) or after image guided, motion-managed proton radiotherapy (Arm 2) both given with concurrent platinum- based chemotherapy.

SECONDARY OBJECTIVES:

I. To compare 2-year progression-free survival (PFS) between the 2 arms. II. To compare the development of grade 3 or higher adverse events definitely, probably, or possibly related to treatment.

III. To compare differences between the two arms in quality of life (QOL) based primarily on the development of shortness of breath at 6 months and secondarily on the development of sore throat at the end of chemoradiotherapy (chemoRT) (as measured by the lung cancer module of the MD Anderson Symptom Inventory [MDASI-Lung]), as well as breathing related functioning impairments as measured by the Shortness Breath Questionnaire [SOBQ].

IV. To compare cost-effectiveness outcomes between the 2 arms. V. To compare pulmonary function changes by treatment arms and response. VI. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery.

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

ARM I: Patients undergo photon beam radiation therapy 5 days per week for a total of 35 fractions and receive either paclitaxel* intravenously (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.

ARM II: Patients undergo proton beam radiation therapy 5 days per week for a total of 35 fractions and receive either paclitaxel* and carboplatin* or etoposide and cisplatin as in Arm I.

*In both arms, patients who receive paclitaxel and carboplatin must complete consolidation therapy.

CONSOLIDATION THERAPY: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4-8 weeks, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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;
    • 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) >= 1.0 Liter or >= 40% 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
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
  • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 1.5 upper limit of normal
  • Total bilirubin =< 1.5 upper limit of normal
  • Serum creatinine < 1.5 mg/dL or calculated creatinine clearance >= 50 mL/min estimated by the Cockcroft-Gault formula
  • Peripheral neuropathy =< grade 1 at the time of registration
  • Patients with non-malignant pleural effusion are eligible

    • If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:

      • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
      • Exudative pleural effusions are excluded, regardless of cytology;
      • Effusions that are minimal (ie, not visible on chest x-ray) that are too small to safely tap are eligible
  • Patients must have measurable or evaluable disease
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration
  • Women of childbearing potential and male participants must practice adequate contraception
  • Patient must provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • 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
  • Prior systemic chemotherapy for the study cancer; 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 90 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01993810

Locations
United States, Florida
University of Florida Health Science Center Recruiting
Jacksonville, Florida, United States, 32209
Contact: Bradford S. Hoppe    877-686-6009      
Principal Investigator: Bradford S. Hoppe         
University of Florida Health Science Center Recruiting
Jacksonville, Florida, United States, 32209
Contact: Bradford S Hoppe, MD    904-588-1800    bhoppe@floridaproton.org   
Principal Investigator: Bradford S Hoppe, MD         
United States, Illinois
Cadence Cancer Center in Warrenville Recruiting
Warrenville, Illinois, United States, 60555
Contact: Vinai Gondi    630-352-5300      
Principal Investigator: Vinai Gondi         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Noah C. Choi    877-726-5130      
Principal Investigator: Noah C. Choi         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jeffrey D. Bradley    800-600-3606    info@siteman.wustl.edu   
Principal Investigator: Jeffrey D. Bradley         
Barnes-Jewish West County Hospital Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Jeffrey D. Bradley    800-600-3606    info@siteman.wustl.edu   
Principal Investigator: Jeffrey D. Bradley         
United States, New Jersey
Memorial Sloan Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
ProCure Proton Therapy Center-Somerset Active, not recruiting
Somerset, New Jersey, United States, 08873
United States, New York
Memorial Sloan Kettering Cancer Center Commack Recruiting
Commack, New York, United States, 11725
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
Memorial Sloan-Kettering Cancer Center Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
Memorial Sloan-Kettering Cancer Center Sleepy Hollow Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
Memorial Sloan-Kettering Cancer Center West Harrison Recruiting
West Harrison, New York, United States, 10604
Contact: Abraham J. Wu    212-639-7202      
Principal Investigator: Abraham J. Wu         
United States, Pennsylvania
University of Pennsylvania/Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Charles B. Simone    215-746-7406      
Principal Investigator: Charles B. Simone         
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Maria Werner-Wasik    215-955-6084      
Principal Investigator: Maria Werner-Wasik         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Quynh-Nhu Nguyen    713-792-3245      
Principal Investigator: Quynh-Nhu Nguyen         
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Zhongxing Liao Radiation Therapy Oncology Group
  More Information

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01993810     History of Changes
Other Study ID Numbers: RTOG 1308  NCI-2013-01850  RTOG 1308  RTOG-1308  U10CA021661 
Study First Received: November 12, 2013
Last Updated: June 10, 2016
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
Non small cell lung cancer
NSCLC
proton radiotherapy

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Etoposide
Etoposide phosphate
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016