Surgical Nivolumab And Ipilimumab For Recurrent GBM

NCT04606316 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-494
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 4

Brief Summary

This research trial is studying the safety and effectiveness of nivolumab in combination with ipilimumab and surgery when used in the treatment of recurrent glioblastoma. The names of the study drugs involved in this study are:

• Nivolumab
• Ipilimumab
• Placebo (IV solution with no medicine)
• Zr-89 Crefmirlimab berdoxam (optional sub-study)

Conditions

Glioblastoma; GBM; Glioblastoma Multiforme; Grade IV Astrocytoma

Keywords

Glioblastoma; GBM; Glioblastoma Multiforme; Grade IV Astrocytoma

Outcome Measures

Primary Outcomes (2)

• Tumor Infiltrating T Lymphocyte (TIL) Density

  TIL density will be assessed and compared between the three arms using the Two-sample t-Test.

  24 Months

• Safety of Study Drug Therapy

  Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety will be assessed by quantifying the toxicities and grades experienced by participants who have received at least one dose of study treatment.

  24 Months

Secondary Outcomes (2)

• Cell Cycle-Related Genetic Signature within the Tumor Microenvironment

  24 months

• Percentage of Progression Free Survival (PFS-6)

  24 months

Study Arms (3)

Nivolumab and Ipilimumab Before and After Surgery

EXPERIMENTAL

One dose of nivolumab plus ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks.

Drug: Nivolumab; Drug: Ipilimumab; Procedure: Surgery

Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab After Surgery

EXPERIMENTAL

One dose of nivolumab plus placebo-ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks.

Drug: Nivolumab; Drug: Ipilimumab-Placebo; Procedure: Surgery

Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

EXPERIMENTAL

One dose of placebo-nivolumab plus placebo-ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks

Drug: Nivolumab-Placebo; Drug: Nivolumab; Drug: Ipilimumab-Placebo; Drug: Ipilimumab; Procedure: Surgery

Interventions

Nivolumab-Placebo DRUG

Intravenous (IV) solution that has no therapeutic effect, used as a control in testing investigational drug. One dose is received prior to surgery.

Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

Nivolumab DRUG

Given as intravenous (IV) infusion into a vein.

Also known as: Opdivo

Nivolumab and Ipilimumab Before and After Surgery; Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab After Surgery; Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

Ipilimumab-Placebo DRUG

Intravenous (IV) solution that has no therapeutic effect, used as a control in testing investigational drug. One dose is received prior to surgery.

Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab After Surgery; Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

Ipilimumab DRUG

Given as intravenous (IV) infusion into a vein.

Also known as: Yervoy

Nivolumab and Ipilimumab Before and After Surgery; Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

Surgery PROCEDURE

Treatment of disease or injury by cutting, abrading, suturing, or otherwise physically changing body tissues and organs.

Also known as: Resection

Nivolumab and Ipilimumab Before and After Surgery; Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab After Surgery; Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically confirmed World Health Organization Grade IV IDH wildtype glioblastoma or variants including gliosarcoma or IDH wildtype glioma with molecularly features of glioblastoma.
• Previous first line therapy with at least radiotherapy.
• Patients must be undergoing surgery that is clinically indicated as determined by their care providers.
• Be at first or second relapse. Note: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy).
• Participants must have shown unequivocal evidence for tumor progression by MRI per RANO criteria.
• Participants must have confirmation of availability of sufficient tissue from prior surgery revealing glioblastoma or variants for submission following registration. The following amount of tissue is required:
• formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) OR
• FFPE unstained slides (5 μm thick)
• An interval of at least 12 weeks from the completion of radiation therapy to registration unless there is unequivocal histologic confirmation of tumor progression.
• An interval of at least 4 weeks (to registration) between prior surgical resection or one week for stereotactic biopsy.
• From registration, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies (including vaccines). No washout period required from tumor treating fields (TTF).
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a Karnofsky performance status (KPS) ≥ 70.
• MRI within 14 days prior of registration.

You may not qualify if:

• IDH mutation by immunohistochemistry.
• Current or planned participation in a study of an investigational agent or using an investigational device.
• Has a diagnosis of immunodeficiency.
• Has tumor primarily localized to the brainstem or spinal cord.
• Has presence of diffuse leptomeningeal disease or extracranial disease.
• Has received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc.) within six months of registration.
• Has received bevacizumab or aflibercept. VEGFR inhibitors are allowed.
• Requires treatment with high dose systemic corticosteroids defined as dexamethasone \> 2 mg/day or bioequivalent at the time of registration.
• Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
• Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade \> 3 within 6 months of registration.
• Has a known additional malignancy that is progressing or requires active treatment. Those patients whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen will be eligible including, but not limited to, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer not requiring treatment, or in situ cervical cancer that has undergone potentially curative therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active non-infectious pneumonitis.

Sponsors & Collaborators

• Patrick Wen, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Nivolumab; Ipilimumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Y Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The neoadjuvant treatment administered prior to surgery will be blinded. The participants, Sponsor, site investigators, and site staff will not know the treatment administered. An assigned Site Investigational Pharmacist will not be blinded. Designated staff of the DF/HCC Office of Data Quality will be unblinded to facilitate randomization and safety monitoring. Treatment after surgery is not blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: October 24, 2020
• First Posted: October 28, 2020
• Study Start: February 1, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)