Combining Radiosurgery and Nivolumab in the Treatment of Brain Metastases
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|ClinicalTrials.gov Identifier: NCT02978404|
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : August 28, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Clear-Cell Metastatic Renal Cell Carcinoma Non Small Cell Lung Cancer Metastatic Brain Metastases, Adult||Drug: Nivolumab Radiation: Radiosurgery||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||June 2, 2017|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
Experimental: Radiosurgery and Nivolumab
Interventions: Nivolumab (240mg IV q2week) and Radiosurgery (15-20 Gray (Gy) in 1 fraction)
Upon entering this trial, patients with metastatic brain disease(s) will receive Nivolumab (240mg IV q2week). 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.
Nivolumab is administered to patients to a maximum of 1 year.
Up to 10 cubic centimeter of brain metastases will be treated with radiosurgery. The dose of radiosurgery depends on the size of individual metastases.
Other Name: SRS
- 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.
- Treated brain lesions control rate [ Time Frame: 1 year ]Treated brain lesions control will be assessed as per RECIST version 1.1.
- Overall survival after receiving Nivolumab. [ Time Frame: 2 years ]
Overall Survival is assessed at the end of the study at 2 years. A subject will be classified as either alive or dead due to any cause.
The time to event will be calculated as the time from Day 1 until date of death.
Day 1 is the date of 1st treatment consisting of an infusion of Nivolumab.
- Maximum response rate of distant non-irradiated disease [ Time Frame: 1 year ]Response will be assessed as per RECIST version 1.1.
- Progression-free survival [ Time Frame: 1 year ]Response will be assessed as per RECIST version 1.1.
- Correlation between tumor PD-L1 expression and clinical outcomes [ Time Frame: 1 year ]Tumor PD-L1 expression level will be correlated with patient overall response rate, loco-regional recurrence free survival and overall survival.
- Patient quality of life [ Time Frame: 1 year ]Quality of life will be assessed using the the Functional Assessment of Cancer Therapy - General (FACT-G) and the Brain Subscale (FACT-BR) questionnaires. A composite score will be obtained from the score of each subscale. Quality of life decline is the time to the first minimal important difference in the composite score from baseline.
- Neurocognitive function, as measured by the HVLT-R [ Time Frame: 1 Year ]Neurocognitive function will be assessed using the Hopkins Verbal Learning Test - Revised (HVLT-R). Neurocognitive failure is the time to the first failure on the assessments using the Reliable Change Index. Baseline neurocognitive function will be compared to the test results at 1 year using either a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
- Neurocognitive function, as measured by TMT [ Time Frame: 1 year ]Neurocognitive function will be assessed using the Trail Making Test (TMT). Neurocognitive failure is the time to the first failure on the assessments using the Reliable Change Index. Baseline neurocognitive function will be compared to the test results at 1 year using either a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
- Neurocognitive function, as measured by COWA [ Time Frame: 1 Year ]Neurocognitive function will be assessed using the Controlled Oral Word Association (COWA). Neurocognitive failure is the time to the first failure on the assessments using the Reliable Change Index. Baseline neurocognitive function will be compared to the test results at 1 year using either a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
- Acute and late toxicity of SRS + Nivolumab [ Time Frame: 1 year ]
Adverse events will be coded according to MedDRA. The results will be tabulated to examine their frequency, organ systems affected, severity, and relationship to study treatment.
Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs. Investigators will provide their assessment of causality as 1) unrelated, 2) unlikely, 3) possibly related, 4) probably, or 5) definitely related.
- Imaging indicators of response [ Time Frame: 1 year ]Patient response to the treatment will be analysed using the Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02978404
|Contact: Philip Wong, MD, FRCPCfirstname.lastname@example.org|
|Contact: Diane Trudel, RNemail@example.com|
|Centre Hospitalier de l'Université de Montréal||Recruiting|
|Montreal, Quebec, Canada, H2L 4M1|
|Contact: Philip Wong, MD, FRCPC 15148908254 firstname.lastname@example.org|
|Contact: Laura Masucci, MD, FRCPC 15148908254 email@example.com|
|McGill University Health Centre||Not yet recruiting|
|Montreal, Quebec, Canada, H4A 3J1|
|Contact: Valerie Panet-Raymond, MD (514) 934-1934 firstname.lastname@example.org|
|Contact: Marianna Perna 514-934-1934 ext 43191 email@example.com|
|Centre Hospitalier Universitaire de Sherbrooke||Recruiting|
|Sherbrooke, Quebec, Canada, J1H 5N4|
|Contact: Marc-Emile Plourde, MD 819-346-1110 ext 14311 firstname.lastname@example.org|
|Contact: Sophie Couture 819-346-1110 ext 14311 email@example.com|
|Principal Investigator:||Philip Wong, MD, FRCPC||Centre hospitalier de l'Université de Montréal (CHUM)|