Combining Radiosurgery and Nivolumab in the Treatment of Brain Metastases

NCT02978404 | Completed Phase 2 DMC

• 2 other identifiers: 16.206OZM-080
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

Stereotactic radiosurgery (SRS) is increasingly administered as the sole treatment of brain metastases, in order to spare acute and long term side effects associated with whole brain radiotherapy. Local control of SRS treated lesions is good, but patients tend to develop additional brain metastases subsequently. Nivolumab is a modulator of the immune system. Treatment with Nivolumab is associated with an increase in local control and survival in patients with non-small cell lung cancer and clear cell renal cell carcinoma. In the presence of Nivolumab, treatment of brain metastases with SRS may trigger an immune reaction against cancer. Therefore, the combination of SRS with Nivolumab may reduce the development of new brain metastases and improve patient survival. The purpose of this study is to assess the effect of combining Nivolumab and SRS in controlling cancer progression. SRS will be administered to patients while they are receiving Nivolumab.

Conditions

Clear-Cell Metastatic Renal Cell Carcinoma; Non Small Cell Lung Cancer Metastatic; Brain Metastases, Adult; Small Cell Lung Cancer; Melanoma

Keywords

radiosurgery; PD-1; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Intracranial progression-free survival

  To evaluate whether the combination SRS with Nivolumab will improve the intracranial progression-free survival of patients. Response will be assessed as per RECIST version 1.1.

  1 year

Secondary Outcomes (11)

• Treated brain lesions control rate

  1 year

• Overall survival after receiving Nivolumab.

  2 years

• Maximum response rate of distant non-irradiated disease

  1 year

• Progression-free survival

  1 year

• Correlation between tumor PD-L1 expression and clinical outcomes

  1 year

Study Arms (1)

Radiosurgery and Nivolumab

EXPERIMENTAL

Interventions: Nivolumab (240mg IV q2week or 480mg IV q4week) and Radiosurgery (15-20 Gray (Gy) in 1 fraction) Upon entering this trial, patients with metastatic brain disease(s) will receive Nivolumab. One to 2 week after receiving the first dose of Nivolumab, radiosurgery will be delivered at doses ranging from 15 to 20 Gy in 1 fraction to the brain metastases to a maximum volume of 10 cubic centimeter.

Drug: Nivolumab; Radiation: Radiosurgery

Interventions

Nivolumab DRUG

Nivolumab is administered to patients to a maximum of 2 year.

Radiosurgery and Nivolumab

Radiosurgery RADIATION

Up to 10 cubic centimeter of brain metastases will be treated with radiosurgery. The dose of radiosurgery depends on the size of individual metastases.

Also known as: SRS

Radiosurgery and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Men and women, ≥ 18 years of age
• Willing and able to give written informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration
• Radiation Therapy Oncology Group (RTOG) neurological function score of 0-1 within 28 days prior to registration
• Histologic diagnosis of NSCLC, SCLC, Melanoma OR ccRCC
• Stage IV cancer with brain metastases (Patients may have untreated primary disease)
• Presenting with previously un-irradiated brain metastasis (10 cc maximum volume of brain disease based on the diagnostic screening MRI done within 28 days of registration))
• Measurable/evaluable brain disease
• Having received less than 4 lines of prior systemic treatments
• Ability to be treated with either gamma knife or a linear accelerator based radiosurgery system
• Ability to complete neurocognitive exams without assistance
• Ability to complete QOL questionnaires with or without assistance
• Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to registration:
• White Blood Cell (WBC) ≥ 2000/uL
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

You may not qualify if:

• Brain metastasis in the brainstem
• Patients who experienced prior seizures are eligible, however patients should not have had a seizure within 7 days of registration without the use of corticosteroids.
• All other cancer histology other than NSCLC or ccRCC
• Patients who cannot undergo MRI
• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients with a condition requiring systemic treatment with either corticosteroids including steroids used for treating peritumoral edema (\> 50 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with Nivolumab-containing regimen
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of Nivolumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
• History of prior treatment with a CTLA-4, PD-1 or PD-L1 inhibitor, CD137 agonist, or anti-PD-L2.
• Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
• Known history of hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• History of allergy to study drug components.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Brain Neoplasms; Small Cell Lung Carcinoma; Melanoma

Interventions

Nivolumab; Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Philip Wong, MD, FRCPC

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

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: November 21, 2016
• First Posted: December 1, 2016
• Study Start: June 2, 2017
• Primary Completion: January 31, 2021
• Study Completion: December 31, 2023
• Last Updated: June 28, 2024

Record last verified: 2024-06

Locations

CA (4)