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Protocol Details

Phase I Study of Ipilimumab, Nivolumab, and the Combination in Patients with Newly Diagnosed Glioblastoma

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Brain Tumor;
Anti- PD-1 antibody;

Recruitment Keyword(s)



Brain Tumor;
Brain Neoplasm

Investigational Drug(s)


Investigational Device(s)



Drug: Temozolomide (TMZ)
Biological/Vaccine: Ipilimumab
Biological/Vaccine: Nivolumab

Supporting Site

National Cancer Institute


- Glioblastoma is a type of brain cancer. People with this cancer who are not enrolled on a study (clinical trial) are usually treated with radiation and temozolomide. Then they get temozolomide alone. For people who receive this approach for this cancer, fewer than 5 out of 100 have no tumor growth at 5 years. Researchers want to test combinations of ipilimumab and nivolumab, drugs know to enhance immune function, along with temozolomide in people with newly diagnosed glioblastoma.


- To find a safe dose for different drug combinations to treat glioblastoma.


- Adults 18 and older who have glioblastoma.


- All participants will have already received regular treatment for their cancer.

- Participants will be screened with blood tests. These tests will check their liver function. They will also have an EKG, medical history, and physical exam. Tissue samples taken at the time of their brain surgery will be reviewed.

- Participants will be put into one of 2 or 3 groups. Each group will get a different drug combination.

- Participants will keep a pill diary.

- Participants will have monthly blood tests. The tests will check their number of immune cells. The tests will also check endocrine and liver function.

- Participants will be treated for up to 16 months depending on side effects and tumor response.

- After participants finish treatment, they will have periodic exams and brain MRI scans.

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A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

1. Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report;

2. The tumor must be unifocal, confined to the supratentorial compartment and have undergone a gross total or near gross total resection. This will increase the likelihood that the patient will not require corticosteroids or develop pseudoprogression.

3. The FFPE tumor tissue block must be available to be sent for retrospective central pathology review after registration

4. Patients must be registered within 28 days of completion of chemoradiation.

5. History/physical examination within 7 days prior to registration;

6. Patients must have undergone an evaluation by MRI within 35 days of completing radiation and must also be within 7 days prior to registration. MRI must NOT demonstrate tumor progression, but patients with imaging changes consistent with pseudo-progression, stable neurologic function and not needing corticosteroid treatment are eligible.

7. Age greater then or equal to 18;

8. The trial is open to both genders;

9. Karnofsky performance status greater than or equal to 70 within 7 days prior to registration;

10. Adequate hematologic function based on CBC/differential within 7 days prior to registration defined as follows:

-Absolute neutrophil count greater than or equal to 1,500 cells/mm3;

-Platelet count greater than or equal to 100,000 cells/mm3

-Hgb greater than 9 g/dL (can be achieved with transfusion)

11. Adequate renal function within 7 days prior to registration defined as follows:

- BUN less than orequal to 30 mg/dl and

-Serum creatinine less tham or equal to 1.7 mg/dl

12. Adequate hepatic function within 7 days prior to registration defined as follows:

-Total bilirubin (except patients with Gilbert s Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) less than or equal to 2.0 mg/dl and

-ALT and AST less than or equal to 2.5x ULN

13. The patient must have completed chemoradiation (All cohorts) within standards of care established by prior RTOG/NRG Oncology studies as follows:


-Modality: Either 3D or IMRT, or proton therapy is allowed

-Time to Initiation: Radiotherapy must be initiated within or equal to 42 days after surgery.

-Target Volumes: Target volume definition will be based upon postoperativeenhanced MRI. Preoperative imaging should be used for correlation and improved identification, as necessary.

-Dose Guidelines: The initial target volume will be treated to 46 Gy in 23 fractions. After 46 Gy, the conedown or boost volume will be treated to a total of 60 Gy, with seven additional fractions of 2 Gy each (14 Gy boost dose).


-Temozolomide must have been administered continuously from day 1 of radiotherapy to the last day of radiation (+/- 3 days to take into consideration holidays) at a daily oral dose of 75 mg/m2 for a maximum of 49 days (except missed doses due to toxicity).

14. The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.

15. The patient must provide study-specific informed consent prior to study entry.

16. ECHO cardiogram and cardiology consultation required within 7 days prior to registration for patients with a history of congestive heart failure or cardiovascular disease or history of exposure to cardiotoxic agents who are not already excluded.


Patients with one or more of the following conditions are NOT eligible for this study.

1. Definitive clinical or radiologic evidence of progressive disease

2. Prior placement of Gliadel wafer or local brachytherapy

3. Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy

4. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

5. Severe, active co-morbidity defined as follows:

-Unstable angina within the last 6 months prior to registration

- Transmural myocardial infarction within the last 6 months prior to registration

- Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of greater than or equal to 2 mm using the analysis of an EKG performed within 7 days prior to registration

- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration

- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration

- Serious and inadequately controlled cardiac arrhythmia

-Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease

-Evidence of bleeding diathesis or coagulopathy

-Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection.

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

-Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

-Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for additional liver function tests not listed and coagulation parameters are not required for entry into this protocol.

-Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive

-Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity.

-Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or CIDP, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn s, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.

A)Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sj(SqrRoot)(Delta)gren s syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), antithyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.

-Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

6. Pregnancy or lactating females due to possible adverse effects on the developing fetus or infant due to study drug. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.

.7. History of severe hypersensitivity reaction to any monoclonal antibody.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Mark R. Gilbert, M.D.
National Cancer Institute (NCI)

Matthew R. Lindsley, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13C436
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6534

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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