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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 140
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab
• Last Updated: 2017-04-19

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 size5 cm butN0M0).

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(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 sizeN0M0) or selected stage IIa disease (T2 [tumor size >5 cm butpoor 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(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*Total Bilirubintotal 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.