An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma

NCT02648997 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: 15-490CA209-324
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in this study are nivolumab and ipilimumab.

Conditions

Meningiomas

Keywords

Atypical Meningioma; Anaplastic Meningioma

Outcome Measures

Primary Outcomes (1)

• Number of Participants Without Disease Progression At Six Months Following Initiation Of Study Therapy

  To evaluate the anti-tumor activity for single-agent nivolumab (cohort 1) or nivolumab plus ipilimumab following radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma.

  6 months

Secondary Outcomes (4)

• Both Cohorts: Median Progression-Free Survival

  2 years

• Both Cohorts: Median Overall Survival

  2 years

• Both Cohorts: Objective Radiologic Response Rate

  2 years

• Both Cohorts: Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0.

  2 years

Other Outcomes (6)

• Evaluate Circulating Immune Cell Subsets and Cytokines as Systemic Immune Correlative Markers

  2 years

• Evaluate Archival Tumor Expression of PD-L1 and PD-1 Expressing Tumor Infiltrating Lymphocytes

  2 years

• Evaluate Archival Tumor Expression of Immune Gene Expression Signature Utilizing the Nanostring Assay

  2 years

Study Arms (3)

Cohort 1 (original cohort): Nivolumab Monotherapy

EXPERIMENTAL

Nivolumab monotherapy (240 mg every 2 weeks)

Drug: Nivolumab - 240 mg

Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab

EXPERIMENTAL

* External Beam RT (IMRT, 3D-CRT, or proton-beam radiation therapy) * Followed by 4 cycles of Nivolumab (1 mg/kg every 3 weeks) + Ipilimumab (3 mg/kg every 3 weeks) * Followed by Nivolumab monotherapy (480 mg every 4 weeks).

Drug: Nivolumab - 240 mg; Drug: Nivolumab - 480 mg; Radiation: External Beam RT; Drug: Nivolumab - 1 mg/kg; Drug: Ipilimumab - 3 mg/kg

Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

EXPERIMENTAL

* External Beam RT (IMRT, 3D-CRT, or proton-beam radiation therapy) * Followed by 4 cycles of Nivolumab (3 mg/kg every 3 weeks) + Ipilimumab (1 mg/kg every 3 weeks) * Followed by Nivolumab monotherapy (480 mg every 4 weeks).

Drug: Nivolumab - 240 mg; Drug: Ipilimumab - 1 mg/kg; Drug: Nivolumab - 480 mg; Drug: Nivolumab - 3 mg/kg; Radiation: External Beam RT

Interventions

Nivolumab - 1 mg/kg DRUG

1 mg/kg every 3 weeks

Also known as: Opdivo, BMS-936558, ONO-4538

Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab

Ipilimumab - 3 mg/kg DRUG

3 mg/kg every 3 weeks

Also known as: BMS-734016, MDX010, MDX-CTLA4

Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab

Nivolumab - 240 mg DRUG

240 mg every 2 weeks

Also known as: Opdivo, BMS-936558, ONO-4538

Cohort 1 (original cohort): Nivolumab Monotherapy; Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab; Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

Ipilimumab - 1 mg/kg DRUG

1 mg/kg every 3 weeks

Also known as: BMS-734016, MDX010, MDX-CTLA4

Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

Nivolumab - 480 mg DRUG

480 mg once every 4 weeks

Also known as: Opdivo, BMS-936558, ONO-4538

Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab; Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

Nivolumab - 3 mg/kg DRUG

3 mg/kg every 3 weeks

Also known as: Opdivo, BMS-936558, ONO-4538

Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

External Beam RT RADIATION

IMRT, 3D-CRT, or proton-beam radiation therapy

Cohort 2 (Dose Level 0): Nivolumab in Combination with Ipilimumab; Cohort 2 (Dose Level 0A): Nivolumab in Combination with Ipilimumab

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 WHO grade I, II or III meningioma that is progressive or recurrent. Metastatic meningiomas are allowed. Participants with grade I tumors must have failed radiation therapy.
• Prior therapy:
• There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents.
• Patients may have been treated with standard external beam radiation or radiosurgery in any combination, however, an interval of ≥ 12 weeks (84 days) must have elapsed from the completion of the radiation therapy to start of study therapy unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line).
• In addition, there must be subsequent evidence of tumor progression after completion of radiation therapy (grade I tumors only)
• An interval of ≥ 28 days and full recovery (no ongoing safety issues) from surgical resection
• An interval of ≥ 7 days from stereotactic biopsy;
• For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas) or biologic therapies.
• Be 18 years of age on day of signing informed consent.
• Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A).
• Participants must demonstrate adequate organ and marrow function as defined below (all screening labs to be performed within 14 days of treatment initiation):
• White blood cell (WBC) ≥ 2000/mm3
• Absolute neutrophil count (ANC) ≥ 1,000/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 gm/dl

You may not qualify if:

• Current or planned participation in a study of an investigational agent or using an investigational device.
• Tumors that are primarily localized to the brainstem or spinal cord;
• Evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans;
• Prior Therapy:
• Prior treatment with systemic immunosuppressive treatments, aside from systemic dexamethasone therapy for cerebral edema, such as methotrexate, chloroquine, azathioprine, etc. within 3 months of start of study therapy;
• Prior treatment with interstitial brachytherapy within 6 months of start of study therapy;
• All patients: Previous treatment with PD-1 or PD-L1 directed therapy;
• Cohort 2 patients: Previous treatment with CTLA-4 directed therapy;
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment, or anticipation of need for major surgical procedure during the course of the study;
• Minor surgical procedure (eg, stereotactic biopsy within 7 days of first study treatment; placement of a vascular access device within 2 days of first study treatment);
• Other Meds:
• Participants who are receiving any other investigational agents.
• Immunosuppressive medications / steroids:
• Subject must not require high dose systemic corticosteroids defined as dexamethasone \> 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks prior to Day 1of study therapy;
• Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Meningioma

Interventions

Nivolumab; Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: David A. Reardon, MD (Clinical Director, Center for Neuro-Oncology)
• Organization: Dana-Farber Cancer Institute

david_reardon@dfci.harvard.edu

617-632-2166

Study Officials

• David A Reardon, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: After completion of accrual to Cohort 1, we opened accrual to Cohort 2.

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 7, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 26, 2026
• Results First Posted: January 26, 2026

Record last verified: 2026-01

Locations

US (1)