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Trial record 3 of 4 for:    071102

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04396860
Recruitment Status : Recruiting
First Posted : May 21, 2020
Last Update Posted : December 2, 2020
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 20, 2020
First Posted Date  ICMJE May 21, 2020
Last Update Posted Date December 2, 2020
Actual Study Start Date  ICMJE August 6, 2020
Estimated Primary Completion Date August 23, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
  • Progression-free survival (PFS) (Phase II) [ Time Frame: From randomization to disease progress or death, assessed up to 4 years ]
    PFS will be defined as time from randomization to disease progress or death. This 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 study, the updated Response Assessment in Neuro-Oncology Criteria (RANO) criteria.
  • Overall survival (OS) (Phase III) [ Time Frame: From randomization to death from any cause, assessed up to 4 years ]
    OS will be defined as time from randomization to death from any cause. 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
  • PFS for the entire cohort (Phase II/III) [ Time Frame: At 2 year ]
    PFS curves will be estimated via the Kaplan-Meier method and a stratified log-rank test.
  • OS proportion [ Time Frame: 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.
  • Comparative frequency of specific adverse events of interest [ Time Frame: 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).
  • Frequency summaries for all adverse event types [ Time Frame: 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.
  • Patient reported symptom burden [ Time Frame: 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.
  • Neurocognitive function (NCF) [ Time Frame: Up to 4 years ]
  • Patient-reported toxicity outcomes [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
  • PFS for the entire cohort (Phase II/III) [ Time Frame: At 2 year ]
    PFS curves will be estimated via the Kaplan-Meier method and a stratified log-rank test.
  • OS proportion [ Time Frame: 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.
  • Comparative frequency of specific adverse events of interest [ Time Frame: 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).
  • Frequency summaries for all adverse event types [ Time Frame: 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.
  • Patient reported symptom burden [ Time Frame: 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.
  • Neurocognitive function (NCF) [ Time Frame: Up to 4 years ]
  • Patient-reported toxicity outcomes [ Time Frame: 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. Statistical models will be used to estimate treatment effects adjusting for patient and tumor characteristics that may be imbalanced by arm, or suggest a differential treatment effect by characteristic (e.g., treatment-covariate interactions). The Cox proportional hazards regression model will be the principal approach, however, in the case that the proportional hazards assumption is inadequately met, other modeling approaches will be applied as appropriate.
  • Serial Liquid biopsy of TERT [ Time Frame: At baseline and before odd numbered cycles ]
    Will be assessed to detect progression. Response is assessed by on changes in contrast enhancement and/or T2/fluid attenuated inversion recovery (FLAIR) hyperintensity on magnetic resonance imaging (MRI) which can reflect changes that are not specific for tumor progression
Current Other Pre-specified Outcome Measures
 (submitted: July 28, 2020)
  • OS (if the study discontinues in phase II) [ Time Frame: At the end of phase II of study ]
  • Tumor biomarker analyses [ Time Frame: Up to 4 years ]
    Will assess PD-L1 expression and mutational burden expression specifically.
  • MGMT protein expression [ Time Frame: 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.
Original Other Pre-specified Outcome Measures
 (submitted: May 20, 2020)
  • OS (if the study terminates in phase II) [ Time Frame: At the end of phase II of study ]
  • Tumor biomarker analyses [ Time Frame: Up to 4 years ]
    Will assess PD-L1 expression and mutational burden expression specifically.
  • MGMT protein expression [ Time Frame: 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.
  • Peripheral blood immunologic profiles [ Time Frame: At baseline and before odd numbered cycles ]
    Immunologic profile changes will be modeled as time-dynamic covariates in relation to OS, PFS, and 2-year OS rate.
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary This phase II/III trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy plus 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. Immunotherapy with monoclonal antibodies, 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. Giving radiation therapy with ipilimumab and nivolumab lengthen the time without brain tumor from returning or growing and extend patients life compared to usual treatment of radiation therapy and chemotherapy.
Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

II. 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.

III. 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.

IV. 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.

V. 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.

VI. 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:

I. 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.

III. 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 over 30 fractions for 5 days per week (Monday-Friday) and 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 over 30 fractions for 5 days per week (Monday-Friday) for 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gliosarcoma
  • MGMT-Unmethylated Glioblastoma
Intervention  ICMJE
  • Biological: Ipilimumab
    Given IV
    Other Names:
    • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
    • BMS-734016
    • MDX-010
    • MDX-CTLA4
    • Yervoy
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
  • 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 Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • Energy Type
    • 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
Study Arms  ICMJE
  • Active Comparator: Arm I (radiation therapy, temozolomide)
    Patients undergo radiation therapy over 30 fractions for 5 days per week (Monday-Friday) and 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.
    Interventions:
    • Device: NovoTTF-100A Device
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
    • Drug: Temozolomide
  • Experimental: Arm II (radiation therapy, ipilimumab, nivolumab)
    Patients undergo radiation therapy over 30 fractions for 5 days per week (Monday-Friday) for 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.
    Interventions:
    • Biological: Ipilimumab
    • Biological: Nivolumab
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
Publications * Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2020)
485
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 23, 2024
Estimated Primary Completion Date August 23, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 NRG Oncology biospecimen bank 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 and stratification 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
  • Contrast-enhanced brain MRI within 72 hours after surgery

    • Magnetic resonance imaging (MRI) with Axial T2 weighted FLAIR {preferred} 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
  • 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
  • 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.)
  • 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 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 72 hours 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 biopsy or 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. These include but are not limited to: patients with a history of immune-related neurologic disease, central nervous system (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:

      • Vitiligo
      • Endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids
      • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04396860
Other Study ID Numbers  ICMJE NCI-2020-03404
NCI-2020-03404 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-BN007 ( Other Identifier: NRG Oncology )
NRG-BN007 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."
URL: https://grants.nih.gov/policy/sharing.htm
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE NRG Oncology
Investigators  ICMJE
Principal Investigator: Andrew B Lassman NRG Oncology
PRS Account National Cancer Institute (NCI)
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP