Trial of Nivolumab With Radiation or Nivolumab and Ipilimumab With Radiation for the Treatment of Intracranial Metastases From Non-Small Cell Lung Cancer

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 80
• Participant gender: Both

Summary

There are 2 parts to this research study: Part 1 (dose escalation) and Part 2 (dose expansion).

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of nivolumab that can be given either with radiation therapy alone or in combination with radiation and ipilimumab, in participants with NSCLC. The goal of Part 2 of this study is to learn if the dose of nivolumab found in Part 1 when given with radiation therapy and ipilimumab can help to control the disease.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab
• Last Updated: 2016-12-19

Criteria

Inclusion Criteria:

1. Pathologically confirmed non-small lung cancer.

2. Stage IV metastatic disease with intracranial disease visible with magnetic resonance image (MRI).

3. At least one brain lesion size >/=0.3 cm in the longest axis amenable to radiation therapy (either via SRS or WBRT)

4. Be willing and able to provide written informed consent/assent for the trial.

5. Be >/= 18 years of age on day of signing informed consent

6. Have a performance status of 0 or 1 on the ECOG Performance Scale.

7. Demonstrate adequate organ function as defined in the table below, all screening labs should be performed 28 days prior to study registration up to the first dose of study drug.

8. Adequate Organ Function Laboratory Values: HEMATOLOGICAL=Absolute neutrophil count (ANC) >/=1,000 /mcL; Platelets >/= 100,000 /mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L. RENAL=Serum creatinine or Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)or >/= 40 mL/min CrCl using the Cockcroft-Gault Formula. HEPATIC=Serum total bilirubintotal bilirubin <3.0 mg/dl) or Direct bilirubinbilirubin levels > 1.5 x ULN; aspartate aminotransferase (AST (SGOT)) and alanine aminotransferase (ALT (SGPT))metastases

9. Inclusion #8 (continued): COAGULATION=International Normalized Ratio (INR) or Prothrombin Time (PT)as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Activated Partial Thromboplastin Time (aPTT)receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 24 hours of study enrollment up to administration of the dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 31 weeks after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year

12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 31 weeks after the last dose of study therapy.

13. We will allow prior radiation to other sites, with no washout period, prior to study entry as long as the high dose regions of the prior and proposed radiation fields do not overlap. In patients where the prior high dose area would overlap with the high dose area of the intended radiation, a 4 month washout period will be required. The safety of such treatment will be at discretion of the treating radiation oncologist.

14. Prior CNS radiation is allowed as long as cumulative radiation doses do not exceed tolerance of critical structures as judged by the treating radiation oncologist.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.

2. Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.

3. Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, whichever is shorter, prior to study Day 1 or who has not recovered (i.e.,baseline) from adverse events due to agents administered more than 4 weeks earlier.

4. Has had prior chemotherapy or targeted small molecule therapy within 3 weeks prior to administration of the study drug or who has not recovered (i.e.,baseline) from adverse events due to a previously administered agent. *Note: Subjects with permanentthrough routine medical management (e.g. thyroid replacement for hypothyroidism), are an exception to this criterion and may qualify for the study. *Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. *Note: Subjects with clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study.

5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy

6. Has known carcinomatous meningitis (also known as leptomeningeal disease).

7. Has an active infection requiring intravenous systemic therapy or hospital admission.

8. Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.

10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

11. Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.

12. Has received a live vaccine 30 days prior to the first dose of trial treatment.

13. Has experienced Grade 4 toxicity on treatment with prior radiation.

14. Has experienced Grade 3-4 intracranial toxicity (hypophysitis or CNS toxicity) with either prior intracranial radiation, anti programmed cell death-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy.

15. Is taking > 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required > 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment.

16. Tumor exhibits epidermal growth factor receptor (EGFR) mutations or ALK re-arrangement that qualifies the patient for treatment with a systemic agent targeting these mutations.

17. Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody

18. Previous CNS surgery within 2 weeks of enrollment, with the exception of biopsy.

19. Unable or unwilling to tolerate an intracranial MRI.

20. Prior systemic therapy utilizing an anti CTLA-4 or PD-1 agent.

21. In the first 5 patients enrolled in treatment groups on part B of this study (receiving combination ipilimumab and nivolumab), patients may have had 1-0 prior lines of systemic therapy after being diagnosed with metastatic disease. This restriction will be lifted in all subsequent cohorts of patients treated on part B.