Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma

NCT03367715 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-00218
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, phase II trial of nivolumab, ipilimumab and short-course radiation therapy in adult patients with newly diagnosed, MGMT unmethylated GBM with the primary objective of determining the overall survival at 1 year.

Conditions

MGMT-unmethylated Glioblastoma (GBM); GBM

Outcome Measures

Primary Outcomes (1)

• 1-year Overall Survival (OS)

  Survival rate is defined as the percentage of participants who survived at 1 year (from either the date of diagnosis or the start of treatment for a disease)

  1 year

Secondary Outcomes (2)

• Median Overall Survival (OS)

  3 years

• Median Progression Free Survival (PFS)

  3 years

Study Arms (1)

Nivolumab + Ipilimumab + Short-course radiation therapy

EXPERIMENTAL

within 6 weeks of the first diagnostic surgery for glioblastoma, all subjects will initiate study treatment on Day 1

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiation Therapy (RT)

Interventions

Nivolumab DRUG

study treatment on Day 1 with one dose of nivolumab 3 mg/kg

Nivolumab + Ipilimumab + Short-course radiation therapy

Ipilimumab DRUG

study treatment on Day 1 with one dose of ipilimumab 1mg/kg

Nivolumab + Ipilimumab + Short-course radiation therapy

Radiation Therapy (RT) RADIATION

total dose of 30 Gy, given in 5 consecutive fractions of 6 Gy each fraction.

Nivolumab + Ipilimumab + Short-course radiation therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged ≥18 years.
• Histopathological evidence of glioblastoma or gliosarcoma, WHO grade IV.
• Tumor MGMT promoter DNA not methylated (i.e., unmethylated) by central testing.
• Maximal tumor diameter (including residual tumor and resection cavity if subjects had tumor resection rather than only stereotactic biopsy) of 6.6 cm or less. Maximal tumor size allowed is derived from an estimated maximal radiotherapy planning target volume (PTV) of 150 cm3.
• Subjects must not have received any prior standard or investigational anti-tumor therapy other than surgery and must not intend to receive any standard or investigational anti-tumor therapy other than the study regimen.
• Karnofsky performance status (Appendix 2) of ≥60.
• Availability of a paraffin-embedded or frozen tumor-tissue block with a minimum of 1 cm2 of tumor surface area, or 20 unstained slides from the glioblastoma tissue specimen if a tumor block cannot be submitted.
• Subjects must start study agent within 6 weeks from the first diagnostic surgery for glioblastoma.
• An interval of at least 2 weeks for surgical resection and 1 week for stereotactic biopsy from the start of study treatment.
• A contrast-enhanced MRI must be obtained within 7 days of the first dose of study treatment.
• Adequate hematologic, hepatic, and renal function defined by
• White blood cell count ≥ 2.0 x 109/L
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin \> 9 g/dL

You may not qualify if:

• Prior use of any standard or investigational anti-tumor therapy other than surgery
• Planned participation in another study of an investigational agent or investigational device or planned use of any other agent or therapeutic device intended for therapy of glioma.
• Prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Primary brainstem or spinal cord tumor.
• Diffuse leptomeningeal gliomatosis.
• Known mutation of the IDH1 or IDH2 genes in the tumor, since glioblastomas with these mutations have different biology and are associated with improved prognosis.
• Systemic treatment with either immunosuppressive doses of corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
• Subjects on a standard high-dose steroid taper after craniotomy or stereotactic biopsy may have received a higher dose of corticosteroids within 14 days of registration, however must be at a dose \< 10 mg daily prednisone or bioequivalent per day within 5 days prior to initiation of study drug.
• Administration of steroids through a route known to result in a minimal systemic exposure \[i.e., intranasal, intraocular, inhaled, topical, or local injection (e.g., intra-articular injection) corticosteroids (\<5% of body surface area)\] are permitted in the absence of active autoimmune disease.
• Subjects requiring adrenal replacement with corticosteroids are eligible if the steroids are at doses ≤ 10 mg prednisone or bioequivalent per day in the absence of active autoimmune disease.
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
• a.Patients with diabetes type I, vitiligo, residual hypo- or hyperthyroidism due to autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic immunosuppressive treatment, or autoimmune conditions not expected to recur in the absence of an external trigger.
• Prior organ transplantation, including allogeneic stem cell transplantation.
• Known history of, or any evidence of active, non-infectious pneumonitis within the last 5 years.
• Known severe (NCI-CTCAE v4.03 Grade 3 or 4) infusion-related allergy or acute hypersensitivity reaction attributed to any monoclonal antibody, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Radiotherapy

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sylvia Kurz, MD, PhD
• Organization: NYU Langone Health - Perlmutter Cancer Center

Sylvia.Kurz@nyulangone.org

212-731-6267

Study Officials

• Andrew Chi, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Sylvia Kurz, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Erik Sulman, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 11, 2017
• Study Start: February 7, 2018
• Primary Completion: May 20, 2021
• Study Completion: March 17, 2022
• Last Updated: July 1, 2022
• Results First Posted: July 1, 2022

Record last verified: 2022-06

Locations

US (1)