Nivolumab and Radiation Therapy With or Without Ipilimumab in Treating Patients With Brain Metastases From Non-small Cell Lung Cancer
Phase I/II Trial of Nivolumab With Radiation or Nivolumab and Ipilimumab With Radiation for the Treatment of Intracranial Metastases From Non-Small Cell Lung Cancer
2 other identifiers
interventional
80
1 country
1
Brief Summary
This phase I/II trial studies the side effects and best dose of nivolumab when giving together with stereotactic radiosurgery or whole brain radiotherapy with or without ipilimumab and to see how well they work in treating patients with non-small cell lung cancer that has spread to the brain. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Radiation therapy, such as whole-brain radiotherapy, uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab together with stereotactic radiosurgery or whole brain radiotherapy with or without ipilimumab may work better in treating patients with non-small cell lung cancer that has spread to the brain.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 26, 2016
CompletedFirst Posted
Study publicly available on registry
March 2, 2016
CompletedStudy Start
First participant enrolled
December 16, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
November 10, 2025
November 1, 2025
11 years
February 26, 2016
November 5, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Recommended phase 2 dose (RP2D) of nivolumab defined as the probability of > 15% intracranial or > 30% extracranial dose limiting toxicities (DLT) (Phase I)
Assessed using a Bayesian model.
Up to 6 weeks
RP2D of nivolumab in combination with ipilimumab defined as the probability of > 15% intracranial or > 30% extracranial DLT (Phase I)
Assessed using a Bayesian model.
Up to 8 weeks
Intracranial progression free survival (PFS) (Phase II)
Up to 4 months
Secondary Outcomes (1)
Neurocognitive changes assessed by the Hopkins Verbal Learning Revised (HVLT-R) total recall test (Phase II)
1 month after radiation to 3 years
Study Arms (4)
Group A (nivolumab, SRS)
EXPERIMENTALPatients receive nivolumab IV over 90 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.
Group B (nivolumab, WBRT)
EXPERIMENTALPatients then receive nivolumab as in Group A. Patients undergo WBRT once daily for 10 days.
Group C (nivolumab, ipilimumab, SRS)
EXPERIMENTALPatients receive nivolumab as in Group A and ipilimumab IV over 90 minutes every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.
Group D (nivolumab, ipilimumab, WBRT)
EXPERIMENTALGROUP D: Patients receive nivolumab as in Group A and ipilimumab as in Group C. Patients undergo WBRT once daily for 10 days.
Interventions
Ancillary studies
Given IV
Correlative studies
Given IV
Undergo SRS
Undergo WBRT
Eligibility Criteria
You may qualify if:
- Pathologically confirmed non-small lung cancer
- Stage IV metastatic disease with intracranial disease visible with magnetic resonance image (MRI)
- At least one brain lesion size \>= 0.3 cm in the longest axis amenable to radiation therapy (either via SRS or WBRT)
- Be willing and able to provide written informed consent/assent for the trial
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) \>= 1,000 /mcL (performed 28 days prior to study registration up to the first dose of study drug)
- Platelets \>= 100,000 /mcL (performed 28 days prior to study registration up to the first dose of study drug)
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (performed 28 days prior to study registration up to the first dose of study drug)
- Serum creatinine or measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) or \>= 40 mL/min CrCl using the Cockroft-Gault formula (performed 28 days prior to study registration up to the first dose of study drug)
- Serum total bilirubin =\< 1.5 X ULN (except for subjects with Gilbert syndrome, who may have total bilirubin \< 3.0 mg/dl) or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (performed 28 days prior to study registration up to the first dose of study drug)
- Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase (SGOT)\]) and alanine aminotransferase (ALT \[serum glutamate pyruvate transaminase (SGPT)\]) =\< 3 X ULN or =\< 5 X ULN for subjects with the liver metastases (performed 28 days prior to study registration up to the first dose of study drug)
- International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed 28 days prior to study registration up to the first dose of study drug)
- Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed 28 days prior to study registration up to the first dose of study drug)
- 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
- 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
- +3 more criteria
You may not qualify if:
- 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
- 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
- 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., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- For the nivolumab only arm patients who received anti PD1 or anti PD-L1 therapies will be excluded, for ipilimumab and nivolumab arms patients who received anti PD1 or anti PD L1 therapies will be eligible
- 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., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; \*Note: Subjects with permanent =\< grade 2 toxicities (e.g. neuropathy) or toxicities corrected through 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 =\< grade 2 amylase or lipase elevations abnormalities that have no corresponding clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study
- 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
- Has known carcinomatous meningitis (also known as leptomeningeal disease)
- Has an active infection requiring intravenous systemic therapy or hospital admission
- 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
- 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
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (hepatitis C virus \[HCV\] antibody) indicating acute or chronic infection
- Has received a live vaccine 30 days prior to the first dose of trial treatment
- Has experienced grade 4 toxicity on treatment with prior radiation
- 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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jing Li
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 26, 2016
First Posted
March 2, 2016
Study Start
December 16, 2016
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
November 10, 2025
Record last verified: 2025-11