Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Suspended
• CT.gov ID: NCT04396860
• Collaborator: NRG Oncology (Other)
• Enrollment: 485
• Locations: 286
• Arms: 2
• Anticipated Duration (Months): 48.6
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II/III trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy in combination with immunotherapy with ipilimumab and nivolumab in treating patients with newly diagnosed MGMT unmethylated glioblastoma. Radiation therapy uses high energy photons to kill tumor and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temozolomide, may not work as well for the treatment of tumors that have the unmethylated MGMT. Immunotherapy with monoclonal antibodies called immune checkpoint inhibitors, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is possible that immune checkpoint inhibitors may work better at time of first diagnosis as opposed to when tumor comes back. Giving radiation therapy with ipilimumab and nivolumab may lengthen the time without brain tumor returning or growing and may extend patients' life compared to usual treatment with radiation therapy and temozolomide.

Condition or Disease	Intervention/Treatment	Phase
Gliosarcoma; MGMT-Unmethylated Glioblastoma	Biological: Ipilimumab; Biological: Nivolumab; Device: NovoTTF-100A Device; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Temozolomide	Phase 2/Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs progression-free survival (PFS) versus adding temozolomide to radiotherapy in patients with newly diagnosed glioblastoma (GBM) without MGMT promoter methylation. (Phase II) II. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs overall survival (OS) versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation. (Phase III)

SECONDARY OBJECTIVES:

1. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation for the phase III part of the study.

2. To determine if adding ipilimumab and nivolumab to radiotherapy significantly increases the 2-year overall survival (OS) rate versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation.

3. To evaluate the safety of adding ipilimumab and nivolumab to radiotherapy via comparative frequency between arms of specific adverse events of interest and frequency summaries for all adverse event types.

4. To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on patient reported outcomes (PROs), as measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) in patients with newly diagnosed GBM without MGMT promoter methylation.

5. To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on selected Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) items in patients with newly diagnosed GBM without MGMT promoter methylation.

6. To evaluate the impact of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on neurocognitive function (NCF) in patients with newly diagnosed GBM without MGMT promoter methylation.

EXPLORATORY OBJECTIVES:

1. To explore biomarkers in pre-treatment archival tumor tissue that may predict efficacy of ipilimumab and nivolumab as measured by OS, PFS, and 2-year OS rate, such as but not limited to:

Ia. PDL1 expression Ib. Mutational burden II. To explore (in the two treatment separately) whether the MGMT protein expression correlates with clinical outcomes including OS, PFS, and 2-year OS rate.

1. To evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide orally (PO) daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab intravenously (IV) over 90 minutes once every 4 weeks (Q4W) for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression.

After completion of study treatment, patients are followed up every 3 months for year 1, then every 4 months for year 2, and then every 6 months thereafter.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 485 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II/III Open-Label Study of Ipilimumab and Nivolumab Versus Temozolomide in Patients With Newly Diagnosed MGMT (Tumor O-6-Methylguanine DNA Methyltransferase) Unmethylated Glioblastoma
• Actual Study Start Date: Aug 6, 2020
• Anticipated Primary Completion Date: Aug 23, 2024
• Anticipated Study Completion Date: Aug 23, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (radiation therapy, temozolomide) Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity.	Device: NovoTTF-100A Device; Wear Optune device; Other Names: NovoTTF-100A NovoTTF-100A System NovoTTFields NovoTumor Treatment Fields Optune Optune Device ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Drug: Temozolomide; Given PO; Other Names: CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac TMZ
Experimental: Arm II (radiation therapy, ipilimumab, nivolumab) Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression.	Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy ; Biological: Nivolumab; Given IV; Other Names: BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation

Outcome Measures

Primary Outcome Measures

1. Progression-free survival (PFS) (Phase II) [From randomization to disease progress or death, assessed up to 4 years]

   Analysis will be performed on the intent-to-treat basis. PFS distributions for each treatment group will be estimated via the Kaplan-Meier survival function. Will utilize the "PFS resolution" guidance provided in the ALLIANCE A071102 (NCT02152982) study, the updated Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

2. Overall survival (OS) (Phase III) [From randomization to death from any cause, assessed up to 4 years]

   Analysis will be performed on the intent-to-treat basis. Overall survival distributions for each treatment group will be estimated via the Kaplan-Meier survival function.

Secondary Outcome Measures

1. PFS for the entire cohort (Phase II/III) [Up to 4 years]

   PFS curves will be estimated via the Kaplan-Meier method and a stratified log-rank test.

2. OS proportion [At 2 years]

   2-year OS will be compared between treatment arms, to determine whether the proportion surviving to this landmark is increased in the experimental (ipilimumab [ipi] + nivolumab [nivo]) arm. Estimates will be obtained from the Kaplan Meier curves, and a test comparing the proportion surviving with an appropriate variance term that accounts for censoring (Greenwood's formula) will be used.

3. Comparative frequency of specific adverse events of interest [Up to 4 years]

   Adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE).

4. Frequency summaries for all adverse event types [Up to 4 years]

   Adverse events will be graded according to CTCAE v5.0 and PRO-CTCAE. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. Complementing physician-assessed AEs will be selected PRO-CTCAE symptom items that have demonstrated sensitivity to immunotherapy-related toxicities but do not overlap with MDASI-BT. The following PRO-CTCAE symptom items will be monitored: rash, itching, muscle pain, joint pain, headache, chills, mouth/throat sores, skin dryness, hair loss, cough, taste changes, dizziness, swelling, hot flashes.

5. Patient reported symptom burden [Up to 4 years]

   Will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)-modified. The MDASI-BT consists of 23 symptoms rated on an 11-point ordinal scale (0 to 10) to indicate the presence and severity of the symptom in the last 24 hours, with 0 being "not present" and 10 being "as bad as you can imagine." These interference items include: general activity, mood, work (includes both work outside the home and housework), relations with other people, walking, and enjoyment of life. Complementing MDASI-BT will be selected PRO-CTCAE symptom items that have demonstrated sensitivity to immunotherapy-related toxicities but do not overlap with MDASI-BT.

6. Neurocognitive function (NCF) [Up to 4 years]

7. Patient-reported toxicity outcomes [Up to 4 years]

   Will utilize the PRO-CTCAE to assess the following items: abdominal pain, rash, itching, muscle pain, joint pain, pain and swelling at injection site, headache, chills, mouth/throat sores, skin dryness, hair loss, cough, taste changes, dizziness, swelling, and hot flashes.

Other Outcome Measures

1. OS (if the study discontinues in phase II) [At the end of phase II of study]

2. Tumor biomarker analyses [Up to 4 years]

   Will assess PD-L1 expression and mutational burden expression specifically.

3. MGMT protein expression [Up to 4 years]

   Will assess the prognostic value of MGMT protein expression (in terms of predicting clinical outcomes such as PFS, OS, and 2-year OS rate) in the two treatment arms, separately. In addition, will evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms. Correlation methods and survival modeling will be used to address these questions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION:

• No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)

• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin & eosin (H&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 23. If tissue cannot be received by postoperative calendar day 23, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 6 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be conveyed to NRG Oncology within 10 business days of receipt of tissue. Note: In the event of an additional tumor resection(s), tissue must be received within 23 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection (partial or complete) is required; a limited biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis

• Note: The central pathology review and central MGMT results determine eligibility. Therefore, patients may be offered the opportunity to consent REGARDLESS of local pathology and MGMT results, and consent can occur BEFORE local pathology interpretation is finalized and BEFORE local MGMT testing is conducted

• Contrast-enhanced brain magnetic resonance imaging (MRI) within 3 days after surgery

• MRI with Axial T2 weighted FLAIR or T2 turbo spin echo (TSE)/fast spin echo (FSE) and 3-dimensional (3D) contrast-enhanced T1 sequences are required

• 3D pre contrast-enhanced T1 sequences are strongly suggested

• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception hormonal or barrier method of birth control; or abstinence during and after treatment

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

• PRIOR TO STEP 2 REGISTRATION:

• Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review

• Note: diagnoses of "Molecular glioblastoma" per the Consortium to Inform Molecular and Practical Approaches to Central Nervous System (CNS) Tumor Taxonomy (c-IMPACT-NOW) criteria or "CNS grade 4" per the World Health Organization (WHO) 2021 criteria are NOT relevant

• MGMT promoter without methylation confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or methylated MGMT promoter are excluded. Note: central pathology review and central MGMT results determine eligibility; local pathology or MGMT results cannot be used for eligibility/randomization

• Note: patients with methylated MGMT may be considered for enrollment on NRG-BN011

• IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at step 2.)

• Note: this test is not being performed in real time as part of central review and will not be provided to sites from a centrally performed test

• History/physical examination within 28 days prior to step 2 registration

• Karnofsky Performance Status (KPS) >= 70 within 28 days prior to step 2 registration

• Neurologic function assessment within 28 days prior to step 2 registration

• Hemoglobin >= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable) (within 7 days prior to step 2 registration)

• Leukocytes >= 2,000/mm^3 (within 7 days prior to step 2 registration)

• Absolute neutrophil count >= 1,500/mm^3 (within 7 days prior to step 2 registration)

• Platelets >= 100,000/mm^3 (within 7 days prior to step 2 registration)

• Total bilirubin =< 1.5 x institutional/lab upper limit of normal (ULN) (within 7 days prior to step 2 registration)

• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN (within 7 days prior to step 2 registration)

• Alanine transferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (within 7 days prior to step 2 registration)

• Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50mL/min (if using the Cockcroft-Gault formula) (within 7 days prior to step 2 registration)

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 7 days prior to step 2 registration. Note that it may need to be repeated if not also within 3 days prior to treatment start

• Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes

Exclusion Criteria:

• Prior therapy for tumor except for resection. For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, gamma knife, cyber knife, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery;

• Note that 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent

• Current or planned treatment with any other investigational agents for the study cancer

• Definitive clinical or radiologic evidence of metastatic disease outside the brain

• Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years

• Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields

• Pregnancy and nursing females due to the potential teratogenic effects and potential risk for adverse events in nursing infants

• History of severe hypersensitivity reaction to any monoclonal antibody

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab, nivolumab, or temozolomide

• On any dose of any systemically administered (oral, rectal, intravenous) corticosteroid within 3 days prior to step 2 registration. Inhaled, topical, and ocular corticosteroids are allowed without limitation but must be recorded. Note that treatment with systemically administered corticosteroid after initiating study treatment is allowed as needed

• Patients with known immune impairment who may be unable to respond to anti-CTLA 4 antibody

• History of interstitial lung disease including but not limited to sarcoidosis or pneumonitis

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, defined as New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

• 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, are excluded, as are patients on active immunosuppressive therapy. These include but are not limited to: patients with a history of immune-related neurologic disease, CNS or motor neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as autoimmune vasculitis [e.g., Wegener's Granulomatosis]), systemic lupus erythematosus (SLE), connective tissue diseases (e.g., systemic progressive sclerosis), 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, Hashimoto's thyroiditis, autoimmune hepatitis are excluded because of the risk of recurrence or exacerbation of disease

• Exceptions: patients with a history of the following conditions are not excluded, unless receiving active immunosuppressive therapy:

• Vitiligo

• Type I diabetes

• Rheumatoid arthritis and other arthropathies

• Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA)

• Anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation are also excluded

• Current or planned therapy with warfarin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
4	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
5	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
6	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
7	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
10	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
11	Kaiser Permanente-Ontario	Ontario	California	United States	91761
12	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
13	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
14	Sutter Roseville Medical Center	Roseville	California	United States	95661
15	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
16	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
17	Torrance Memorial Physician Network - Cancer Care	Torrance	California	United States	90505
18	Torrance Memorial Medical Center	Torrance	California	United States	90509
19	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
20	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
21	Porter Adventist Hospital	Denver	Colorado	United States	80210
22	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
23	Parker Adventist Hospital	Parker	Colorado	United States	80138
24	Hartford Hospital	Hartford	Connecticut	United States	06102
25	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
26	Beebe South Coastal Health Campus	Frankford	Delaware	United States	19945
27	Beebe Medical Center	Lewes	Delaware	United States	19958
28	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
29	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
30	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
31	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
32	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
33	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
34	AdventHealth Orlando	Orlando	Florida	United States	32803
35	Augusta University Medical Center	Augusta	Georgia	United States	30912
36	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
37	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
38	Lewis Hall Singletary Oncology Center	Thomasville	Georgia	United States	31792
39	Hawaii Cancer Care - Savio	'Aiea	Hawaii	United States	96701
40	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
41	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii	United States	96701
42	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii	United States	96701
43	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
44	Island Urology	Honolulu	Hawaii	United States	96813
45	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii	United States	96813
46	Queen's Medical Center	Honolulu	Hawaii	United States	96813
47	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
48	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
49	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
50	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
51	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
52	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
53	Castle Medical Center	Kailua	Hawaii	United States	96734
54	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
55	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
56	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
57	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
58	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
59	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
60	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
61	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho	United States	83301
62	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
63	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
64	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
65	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
66	Northwestern University	Chicago	Illinois	United States	60611
67	University of Illinois	Chicago	Illinois	United States	60612
68	Carle on Vermilion	Danville	Illinois	United States	61832
69	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
70	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
71	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois	United States	60115
72	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
73	Crossroads Cancer Center	Effingham	Illinois	United States	62401
74	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
75	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
76	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
77	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
78	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
79	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
80	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
81	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
82	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
83	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
84	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
85	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
86	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
87	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
88	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
89	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
90	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
91	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
92	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
93	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
94	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
95	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
96	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
97	Springfield Clinic	Springfield	Illinois	United States	62702
98	Memorial Medical Center	Springfield	Illinois	United States	62781
99	Carle Cancer Center	Urbana	Illinois	United States	61801
100	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
101	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
102	Illinois CancerCare - Washington	Washington	Illinois	United States	61571
103	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
104	IU Health Methodist Hospital	Indianapolis	Indiana	United States	46202
105	Mary Greeley Medical Center	Ames	Iowa	United States	50010
106	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
107	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
108	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
109	Jennie Edmundson Memorial Hospital	Council Bluffs	Iowa	United States	51502
110	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa	United States	51503
111	Greater Regional Medical Center	Creston	Iowa	United States	50801
112	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
113	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
114	Broadlawns Medical Center	Des Moines	Iowa	United States	50314
115	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
116	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
117	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
118	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
119	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
120	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
121	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
122	Eastern Maine Medical Center	Bangor	Maine	United States	04401
123	MaineHealth Coastal Cancer Treatment Center	Bath	Maine	United States	04530
124	Waldo County General Hospital	Belfast	Maine	United States	04915
125	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
126	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
127	Penobscot Bay Medical Center	Rockport	Maine	United States	04856
128	MaineHealth Cancer Care Center of York County	Sanford	Maine	United States	04073
129	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
130	Maine Medical Partners Neurology	Scarborough	Maine	United States	04074
131	Maine Medical Partners - South Portland	South Portland	Maine	United States	04106
132	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
133	UM Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
134	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland	United States	21044
135	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland	United States	21061
136	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
137	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
138	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan	United States	48114
139	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
140	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan	United States	48188
141	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
142	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan	United States	48118
143	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
144	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
145	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
146	Hurley Medical Center	Flint	Michigan	United States	48503
147	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
148	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
149	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
150	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
151	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
152	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
153	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
154	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
155	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
156	Ascension Saint Joseph Hospital	Tawas City	Michigan	United States	48764
157	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
158	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
159	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
160	Metro Health Hospital	Wyoming	Michigan	United States	49519
161	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan	United States	48197
162	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
163	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
164	Minnesota Oncology - Burnsville	Burnsville	Minnesota	United States	55337
165	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
166	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
167	Unity Hospital	Fridley	Minnesota	United States	55432
168	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota	United States	55369
169	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
170	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
171	Health Partners Inc	Minneapolis	Minnesota	United States	55454
172	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
173	Regions Hospital	Saint Paul	Minnesota	United States	55101
174	United Hospital	Saint Paul	Minnesota	United States	55102
175	Lakeview Hospital	Stillwater	Minnesota	United States	55082
176	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
177	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi	United States	38671
178	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
179	Billings Clinic Cancer Center	Billings	Montana	United States	59101
180	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
181	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
182	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
183	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
184	Nebraska Medicine-Bellevue	Bellevue	Nebraska	United States	68123
185	Cancer Partners of Nebraska - Pine Lake	Lincoln	Nebraska	United States	68516
186	Southeast Nebraska Cancer Center - 68th Street Place	Lincoln	Nebraska	United States	68516
187	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
188	Nebraska Medicine-Village Pointe	Omaha	Nebraska	United States	68118
189	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
190	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
191	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
192	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
193	Morristown Medical Center	Morristown	New Jersey	United States	07960
194	Jersey Shore Medical Center	Neptune	New Jersey	United States	07753
195	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
196	Capital Health Medical Center-Hopewell	Pennington	New Jersey	United States	08534
197	Overlook Hospital	Summit	New Jersey	United States	07902
198	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
199	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
200	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
201	University of Rochester	Rochester	New York	United States	14642
202	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
203	Good Samaritan Hospital Medical Center	West Islip	New York	United States	11795
204	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
205	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina	United States	28210
206	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina	United States	28025
207	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
208	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
209	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
210	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
211	Case Western Reserve University	Cleveland	Ohio	United States	44106
212	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
213	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
214	Dublin Methodist Hospital	Dublin	Ohio	United States	43016
215	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
216	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
217	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
218	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
219	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
220	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
221	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
222	Providence Portland Medical Center	Portland	Oregon	United States	97213
223	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
224	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
225	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
226	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
227	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania	United States	19008
228	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
229	Lancaster General Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania	United States	17601
230	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
231	Forbes Hospital	Monroeville	Pennsylvania	United States	15146
232	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
233	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
234	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
235	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
236	Reading Hospital	West Reading	Pennsylvania	United States	19611
237	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania	United States	15090
238	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina	United States	29730
239	Avera Cancer Institute at Pierre	Pierre	South Dakota	United States	57501
240	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
241	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
242	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
243	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee	United States	38017
244	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee	United States	38120
245	Memorial Hermann Texas Medical Center	Houston	Texas	United States	77030
246	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
247	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah	United States	84003
248	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
249	Logan Regional Hospital	Logan	Utah	United States	84321
250	Intermountain Medical Center	Murray	Utah	United States	84107
251	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
252	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
253	Riverton Hospital	Riverton	Utah	United States	84065
254	Saint George Regional Medical Center	Saint George	Utah	United States	84770
255	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
256	LDS Hospital	Salt Lake City	Utah	United States	84143
257	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
258	University of Vermont Medical Center	Burlington	Vermont	United States	05401
259	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
260	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
261	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
262	VCU Community Memorial Health Center	South Hill	Virginia	United States	23970
263	Virginia Mason Medical Center	Seattle	Washington	United States	98101
264	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington	United States	98684
265	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
266	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
267	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
268	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
269	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
270	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
271	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
272	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
273	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
274	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
275	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
276	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
277	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
278	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
279	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
280	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
281	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
282	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
283	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
284	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
285	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
286	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Andrew B Lassman, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT04396860
• Other Study ID Numbers: NCI-2020-03404; NCI-2020-03404; NRG-BN007; NRG-BN007; U10CA180868
• First Posted: May 21, 2020
• Last Update Posted: Aug 25, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioblastoma; Gliosarcoma; Nivolumab; Ipilimumab; Temozolomide

Study Results

No Results Posted as of Aug 25, 2022