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

Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Clinical Trial

Official title:

Phase III Randomized Trial Comparing Overall Survival After Photon Versus Proton Chemoradiotherapy for Inoperable Stage II-IIIB NSCLC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01993810
• Other study ID #: RTOG 1308
• Secondary ID: NCI-2013-01850RT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 3, 2014
• Est. completion date: October 2025

Study information

• Verified date: October 2023
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. II. To compare the cardiac toxicity and lymphocyte reduction (lymphopenia) definitely, probably, or possibly related to treatment between the 2 arms. 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 not included above that are 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. Patients with non-squamous cell cancera may receive pemetrexed IV and carboplatin IV on every 21 days. ARM II: 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. *In both arms, 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 330
• Est. completion date: October 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• 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
• Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable), obtained within 30 days prior to registration
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) within 30 days prior to registration
• It is highly recommended but not required that SGOT or SGPT be =< 1.5 upper limit of normal
• Total bilirubin =< 1.5 within 30 days prior to registration
• It is highly recommended but not required that total bilirubin be =< 1.5 upper limit of normal
• Serum creatinine < 1.5 mg/dL or calculated creatinine clearance >= 50 mL/min within 30 days prior to registration 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 (i.e, 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, 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage II Non-Small Cell Lung Cancer AJCC v7
• Stage IIA Non-Small Cell Lung Carcinoma AJCC v7
• Stage IIB Non-Small Cell Lung Carcinoma AJCC v7
• Stage III Non-Small Cell Lung Cancer AJCC v7
• Stage IIIA Non-Small Cell Lung Cancer AJCC v7
• Stage IIIB Non-Small Cell Lung Cancer AJCC v7

Intervention

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IV

Biological:
• Durvalumab
Given IV

Drug:
• Etoposide
Given IV
• Paclitaxel
Given IV
• Pemetrexed Disodium
Given IV

Radiation:
• Photon Beam Radiation Therapy
Undergo photon beam radiation therapy
• Proton Beam Radiation Therapy
Undergo proton beam radiation therapy

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Maryland Proton Treatment Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Mass General/North Shore Cancer Center	Danvers	Massachusetts
United States	Tate Cancer Center	Glen Burnie	Maryland
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson Regional Care Center-Katy	Houston	Texas
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Tennessee Cancer Specialists-Dowell Springs	Knoxville	Tennessee
United States	MD Anderson Regional Care Center-Bay Area	Nassau Bay	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	ProCure Proton Therapy Center-Seattle	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York
United States	ProCure Proton Therapy Center-Somerset	Somerset	New Jersey
United States	MD Anderson Regional Care Center-Sugar Land	Sugar Land	Texas
United States	MD Anderson Regional Care Center-The Woodlands	The Woodlands	Texas
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	West Chester Hospital	West Chester	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free survival	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	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.
Secondary	Adverse events	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	From start of treatment to end of follow-up