A Phase II, Multi-centre Study, of Combining Radiosurgery and Nivolumab in the Treatment of Brain Metastases From Non-small Cell Lung Cancer and Renal Cell Cancer
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Clear-Cell Metastatic Renal Cell Carcinoma
- Sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Enrollment
- 26
- Locations
- 4
- Primary Endpoint
- Intracranial progression-free survival
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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-L
- •Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies
Arms & Interventions
Radiosurgery and Nivolumab
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.
Intervention: Nivolumab
Radiosurgery and Nivolumab
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.
Intervention: Radiosurgery
Outcomes
Primary Outcomes
Intracranial progression-free survival
Time Frame: 1 year
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.
Secondary Outcomes
- Overall survival after receiving Nivolumab.(2 years)
- Correlation between tumor PD-L1 expression and clinical outcomes(1 year)
- Patient quality of life(1 year)
- Neurocognitive function, as measured by the HVLT-R(1 Year)
- Neurocognitive function, as measured by TMT(1 year)
- Acute and late toxicity of SRS + Nivolumab(1 year)
- Imaging indicators of response(1 year)
- Treated brain lesions control rate(1 year)
- Progression-free survival(1 year)
- Neurocognitive function, as measured by COWA(1 Year)
- Maximum response rate of distant non-irradiated disease(1 year)