Clinical Trials /

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

NCT01993810

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Comparing Photon Therapy To Proton Therapy To Treat Patients With Lung Cancer
  • Official Title: Phase III Randomized Trial Comparing Overall Survival After Photon Versus Proton Chemoradiotherapy for Inoperable Stage II-IIIB NSCLC

Clinical Trial IDs

  • ORG STUDY ID: RTOG 1308
  • SECONDARY ID: NCI-2013-01850
  • SECONDARY ID: RTOG 1308
  • SECONDARY ID: RTOG-1308
  • SECONDARY ID: RTOG-1308
  • SECONDARY ID: U10CA180868
  • SECONDARY ID: U10CA021661
  • NCT ID: NCT01993810

Conditions

  • 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

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboArm I (photon beam radiation therapy and chemotherapy)
CisplatinAbiplatin, 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, PlatosinArm I (photon beam radiation therapy and chemotherapy)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm I (photon beam radiation therapy and chemotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Arm I (photon beam radiation therapy and chemotherapy)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm I (photon beam radiation therapy and chemotherapy)
Pemetrexed DisodiumAlimta, 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 SaltArm I (photon beam radiation therapy and chemotherapy)

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-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.

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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (photon beam radiation therapy and chemotherapy)Active ComparatorPatients 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.
  • Carboplatin
  • Cisplatin
  • Durvalumab
  • Etoposide
  • Paclitaxel
  • Pemetrexed Disodium
Arm II (proton beam radiation therapy and chemotherapy)ExperimentalPatients 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.
  • Carboplatin
  • Cisplatin
  • Durvalumab
  • Etoposide
  • Paclitaxel
  • Pemetrexed Disodium

Eligibility 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

               -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:From registration until death or last follow-up; analysis occurs after 390 deaths have been reported
Safety Issue:
Description:The time from study registration until death or last follow-up

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description: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
Measure:Adverse events
Time Frame:From start of treatment to end of follow-up
Safety Issue:
Description: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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Radiation Therapy Oncology Group

Last Updated

August 31, 2018