Clinical Trials /

Stereotactic Body Radiation Therapy With or Without Nivolumab in Treating Patients With Stage I-IIA or Recurrent Non-small Cell Lung Cancer

NCT03110978

Description:

This phase II trial studies how well stereotactic body radiation therapy with or without nivolumab works in treating patients with stage I-IIA non-small cell lung cancer or cancer that has come back. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy and nivolumab may work better at treating non-small cell lung cancer.

Related Conditions:
  • Bronchioloalveolar Carcinoma
  • Large Cell Lung Carcinoma
  • Large Cell Lung Neuroendocrine Carcinoma
  • Lung Adenocarcinoma
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trials Comparing Immunotherapy Plus Stereotactic Ablative Radiotherapy (I-SABR) Versus SABR Alone for Stage I or Isolated Lung Parenchymal Recurrent Non-small Cell Lung Cancer: I-SABR
  • Official Title: Phase II Randomized Clinical Trials Comparing Immunotherapy Plus Stereotactic Ablative Radiotherapy (I-SABR) Versus SABR Alone for Stage I or Isolated Lung Parenchymal Recurrent Non-small Cell Lung Cancer: I-SABR - Strategic Alliance | BMS

Clinical Trial IDs

  • ORG STUDY ID: 2016-0737
  • NCT ID: NCT03110978

Conditions

  • Malignant Neoplasms of Respiratory and Intrathoracic Organs
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
NivolumabBMS-936558, OpdivoStereotactic Ablative Radiotherapy (SABR) + Nivolumab

Purpose

The goal of this clinical research study is to learn if adding nivolumab to standard treatment (stereotactic ablative radiotherapy [SABR]) can help to control recurrent (has come back) non-small cell lung cancer (NSCLC).

Detailed Description

      Study Groups:

      If participant is found to be eligible to take part in this study, participant will be
      randomly assigned (as in the flip of a coin) to receive either SABR alone (Group 1) or SABR
      and nivolumab (Group 2). This is done because no one knows if one study group is better, the
      same, or worse than the other group.

      Participant will have an equal chance (50/50) of being assigned to either group. Both
      participant and the doctor will know which treatment participant is receiving.

      Study Drug Administration:

      Participant will receive SABR as part of participant's standard care. The study doctor will
      discuss with participant how SABR will be administered and how often participant will
      receive it.

      If participant is in Group 2, participant will also receive nivolumab by vein over about 30
      minutes within 24 hours before or after participant's SABR treatment and then every 2 weeks
      after that for a total of 7 doses (about 3 months).

      Length of Study Participation:

      Participant will receive SABR over about 1-2 weeks. If participant is in Group 2,
      participant may receive nivolumab for up to 7 doses. Participant will no longer be able to
      take the study drug if the disease gets worse, if intolerable side effects occur, or if
      participant is unable to follow study directions.

      Participation in this study will be over after 5 years.

      Follow-Up:

      After participant completes SABR therapy, participant will be followed every 3 months for 2
      years, then every 6 months for up to 3 years, and then 1 time every year after that. At each
      follow-up visit:

        -  Participant will have a physical exam

        -  Participant will have a CT scan.

        -  At Month 9, participant may have a PET-CT scan. The doctor will tell participant if
           participant will have this scan.

      This is an investigational study. SABR is delivered using FDA approved and commercially
      available methods. Nivolumab is FDA approved and commercially available for the treatment of
      NSCLC. It is considered investigational to use it in combination with SABR to treat NSCLC.

      Up to 140 participants will be take part in this study. All will be enrolled at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Stereotactic Ablative Radiotherapy (SABR)ExperimentalStandard SABR (50 Gy in 4 fx, BED=113 Gy; or, if plans for 50 Gy/4 fx cannot meet normal-tissue dose-volume constraints, 70 Gy in 10 fx, BED=119) to the tumor.
    Stereotactic Ablative Radiotherapy (SABR) + NivolumabExperimentalStandard SABR (50 Gy in 4 fx, BED=113 Gy; or, if plans for 50 Gy/4 fx cannot meet normal-tissue dose-volume constraints, 70 Gy in 10 fx, BED=119) to the tumor. Nivolumab given within 24 hours before or after the first fraction of SABR and then every 2 weeks for a total of 7 doses.
    • Nivolumab

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histological confirmation of NSCLC by either biopsy or cytology will be is required
                 for the primary diagnosis and is recommended for recurrent disease. The following
                 primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma (with or
                 without bronchioloalveolar carcinoma features), large cell carcinoma (with or without
                 neuroendocrine features), neuroendocrine carcinoma (either NSCLC with neuroendocrine
                 features or atypical carcinoids, but not small cell lung carcinoma),
                 bronchioloalveolar cell carcinoma, or non-small cell carcinoma not otherwise
                 specified.
    
              2. Stage I or selected stage IIa according to the 7th version of the IASLC system: stage
                 I (T1 or T2a [tumor size </=5 cm] N0M0) stage IIa (T2 [tumor size >5 cm but </= 7 cm]
                 N0M0).
    
              3. Patients with multiple primary lung tumors (defined below) are eligible: a)
                 synchronous tumors (diagnosed within 6 months [mo]), *different histology, *same
                 histology, *second tumor in different lobed or lung; b) metachronous tumors
                 (diagnosed >6 mo apart), *different histology, *same histology, **second tumor in
                 different lobe or lung, **tumor-free interval of at least 4 years (y).
    
              4. Patients with isolated lung parenchymal recurrent/persistent NSCLC (histology as
                 defined in eligibility criterion 1) after prior definitive surgery or
                 radiotherapy/chemotherapy, when the lesion or lesions are suitable for SABR, are also
                 eligible. Patients with a single metastatic focus in the lung parenchyma with no
                 lesions are also eligible, because this presentation is challenging to distinguish
                 from recurrent disease. Recurrent disease can be in the same lobe or a different lobe
                 but should not abut critical structures (esophagus, brachial plexus, major vessels,
                 heart, spinal cord); should not involve any lymph node; and should not include any
                 other suspicious lesions in the lung or any other locations. Any prior therapy
                 (surgery, radiotherapy, or systemic) must have been completed at least 12 weeks
                 before administration of the study drug.
    
              5. cont'd from inclusion #4: Tumors should be </=7 cm (measured by computed tomography
                 (CT) imaging in the lung window setting) with N0M0; positron emission tomography
                 (PET) imaging is required for restaging (per eligibility criterion 5 below) and any
                 lymph node suspected of harboring tumor should be confirmed by biopsy (per
                 eligibility criterion 6 below).
    
              6. A PET/CT scan is required within 12 weeks from enrollment. Any lymph node suspected
                 of harboring disease based on its shape, size, or PET SUV should be discussed by
                 treating physician and diagnostic radiologist.
    
              7. Patients with medically inoperable stage I disease (T1 or T2a [tumor size </=5 cm]
                 N0M0) or selected stage IIa disease (T2 [tumor size >5 cm but </=7 cm] N0M0) who have
                 poor lung function or other significant cardiovascular or other comorbidity such as
                 diabetes are eligible. Patients with operable disease who choose to have SABR are
                 also eligible. The standard justification for medical inoperability is based on
                 pulmonary function and can include any of the following: baseline FEV1 <50% of
                 predicted value; diffusion capacity <50% of predicted value; baseline hypoxemia or
                 hypercapnia; exercise oxygen consumption <50% of predicted value; severe pulmonary
                 hypertension; severe cerebral, cardiac, or peripheral vascular disease; and severe
                 chronic heart disease.
    
              8. Patients must be >/= 18 years of age.
    
              9. Patients must have a Zubrod performance status score of 0-2 (2 is included here
                 because such patients are typically >70 years old and cannot tolerate surgery).
    
             10. All patients must sign a study-specific consent form
    
             11. All patients (men & women) of childbearing potential should use a method of birth
                 control that is effective for them throughout their participation in this study.
                 Women of childbearing potential should use an adequate contraceptive method to avoid
                 pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five
                 half-lives) after the last dose of investigational drug; must have a negative serum
                 or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human
                 chorionic gonadotropin [HCG]) within 24 hours before the start of nivolumab; and must
                 not be breastfeeding. Men who are sexually active with women of childbearing
                 potential must use a contraceptive method with a failure rate of less than 1% per
                 year; men receiving nivolumab will be instructed to use contraception for 7 months
                 after the last dose of nivolumab. Women who are not of childbearing potential (i.e
                 are postmenopausal or surgically sterile) & azoospermic men do not require
                 contraception.
    
             12. All patients must have adequate organ function as defined below. All screening lab
                 tests should be done within 30 days before study registration and the first dose of
                 study drug. WBC >=2000/uL; Neuts >=1500/uL; PLT >=100x10^3/uL; HGB >9.0g/dL; Serum
                 creatinine <=1.5xULN or creatinine clearance (calculated with the Cockcroft-Gault
                 formula below) ≥40 mL/min: Men: ([l40-age in years] × weight in kg) / (72 × serum
                 creatinine in mg/dL) Women: ([l40-age in years] × weight in kg) / (72 × serum
                 creatinine in mg/dL) × 0.85; AST/ALT <=3xULN; Bili T <=1.5xULN (although patients
                 with Gilbert syndrome can have total bilirubin <3.0 mg/dL)
    
             13. All patients must sign a study-specific consent form.
    
             14. All patients (men & women) of childbearing potential should use method of birth
                 control that is effective for them throughout their participation in this study.
                 Women of childbearing potential should use an adequate contraceptive method to avoid
                 pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five
                 half-lives) after last dose of investigational drug; must have a negative serum or
                 urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human
                 chorionic gonadotropin [HCG]) within 24 hours before the start of nivolumab; and must
                 not be breastfeeding. Men who are sexually active with women of childbearing
                 potential must use a contraceptive method with a failure rate of less than 1% per
                 year; men receiving nivolumab will be instructed to use contraception for 7 months
                 after the last dose of nivolumab. Women who are not of childbearing potential (i.e.,
                 are postmenopausal or surgically sterile) and azoospermic men do not require
                 contraception.
    
             15. All patients must have adequate organ function as defined below. All screening lab
                 tests should be done within 30 days before study registration and the first dose of
                 study drug. *WBC >/= 2000/uL; * Neutrophils >/= 1500/uL; *Platelets >/= 100 x10^3/uL;
                 *Hemoglobin > 9.0 g/dL; *Serum creatinine </= 1.5 x ULN or creatinine clearance
                 (calculated with the Cockcroft-Gault formula below) >/= 40 mL/min: Men ([140 - age in
                 years] x weight in kg)/ (72 x serum creatinine in mg/dL) *Women: ([140 - age in
                 years] x weight in kg) / (72 x serum creatinine in mg/dL) x 0.85 *AST/ALT </=3 x ULN;
                 *Total Bilirubin </= 1.5 x ULN (although patients with Gilbert syndrome can have
                 total bilirubin <3.0 mg/dL)
    
            Exclusion Criteria:
    
              1. Patients with tumors >7 cm or tumors involving the main bronchus or associated
                 vessels or tumors that abut any critical structures (such as esophagus, brachial
                 plexus, heart, mediastinal major vessels) are not suitable for SABR.
    
              2. Patients with direct evidence of regional or distant metastases after appropriate
                 staging studies, or with synchronous non-lung primary or prior non-lung malignancy
                 (other than nonmelanomatous skin cancer or in situ cancer) diagnosed within the past
                 3 years are not eligible. Patients with a history of curable non-lung cancer up to 3
                 years before registration and have been cancer-free for 2 years are eligible.
    
              3. Patients who have received previous immunotherapy with PD1 or CTLA4 antibodies are
                 not eligible.
    
              4. Patients with plans to receive other concomitant local therapy (including standard
                 fractionated radiotherapy and surgery) or other systemic therapy (including
                 chemotherapy, target therapy and other type of immunotherapy or investigative agents)
                 while on this protocol, except at disease progression, are not eligible.
    
              5. Female patients who are pregnant or lactating are not eligible (because treatment
                 involves unforeseeable risks to the embryo or fetus).
    
              6. Patients for whom SABR plans cannot meet the minimum requirement of target coverage
                 and dose-volume constraints of critical structures (see SABR treatment planning
                 section) are not eligible.
    
              7. Patients who have active, known, or suspected autoimmune disease are not eligible.
                 However, patients with vitiligo, type I diabetes mellitus, residual hypothyroidism
                 due to an autoimmune condition that requires only hormone replacement, psoriasis not
                 requiring systemic treatment, or conditions not expected to recur in the absence of
                 an external trigger are permitted to enroll.
    
              8. Patients with a known history of antibodies to human immunodeficiency virus (HIV) -1
                 or -2 are not eligible. Patients with live vaccines.
    
              9. Patients with a positive test for hepatitis B virus surface antigen (HBV sAg) or
                 hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic
                 infection are not eligible.
    
             10. Patients who have a condition requiring systemic treatment with corticosteroids (>10
                 mg daily prednisone equivalents) or other immunosuppressive medications within 14
                 days of study drug administration are not eligible. However, inhaled or topical
                 steroids, adrenal replacement doses, and >10 mg daily prednisone equivalents are
                 permitted in the absence of active autoimmune disease.
    
             11. Patients with allergies or adverse drug reactions to the following are not eligible:
                 *History of allergy to study drug components; *History of severe hypersensitivity
                 reaction to any monoclonal antibody.
    
             12. Patients who have had prior treatment with an anti-PD1, anti-PDL1, anti-PDL2,
                 anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell
                 costimulation or immune checkpoint pathways are not eligible.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Event-Free Survival (EFS)
    Time Frame:2 years
    Safety Issue:
    Description:EFS defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death. EFS time calculated from the randomization date to local recurrence, regional recurrence, distant metastasis, or death due to any cause whichever happens the first.

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:5 years
    Safety Issue:
    Description:OS calculated from the randomization date to death date.
    Measure:Toxicity Related to SABR and Immunotherapy
    Time Frame:3 months
    Safety Issue:
    Description:Toxicity defined as grade 3 or higher Pneumonitis, within 3 months for all the patients treated in each arm.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:M.D. Anderson Cancer Center

    Trial Keywords

    • Malignant neoplasms of respiratory and intrathoracic organs
    • Non-small Cell Lung Cancer
    • NSCLC
    • Squamous cell carcinoma
    • Adenocarcinoma
    • Large cell carcinoma
    • Bronchioloalveolar cell carcinoma
    • Stereotactic ablative radiotherapy
    • SABR
    • Nivolumab
    • BMS-936558
    • Opdivo
    • Immunotherapy

    Last Updated

    April 19, 2017