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Clear-Cell Metastatic Renal Cell CarcinomaPhase 2NCT02978404

Combining Radiosurgery and Nivolumab in the Treatment of Brain Metastases

A Phase 2 study testing Nivolumab and Radiosurgery in people with Clear-Cell Metastatic Renal Cell Carcinoma and Non Small Cell Lung Cancer Metastatic, run by Centre hospitalier de l'Université de Montréal (CHUM) at 4 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Radiosurgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
4 sitesCanada
Study dates
2 Jun 2017to 31 Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Platelets≥ 100 x 109/L
  • Hemoglobin ≥ 90 g/L (may be transfused)
  • Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or Creatinine Clearance ≥ 50 ml/min (calculated -cockcroft-Gault)
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤3 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
  • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (28 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab
  • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of Nivolumab product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception).

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • Centre Hospitalier de l'Université de Montréal

    Montreal, Quebec, H2L 4M1

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • Centre Hospitalier Universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

About this study

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

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.

Being tested
Nivolumab, Radiosurgery
Keywords
radiosurgery, PD-1, Nivolumab
Medical subject headings
Clear-cell metastatic renal cell carcinoma, Brain Neoplasms, Small Cell Lung Carcinoma, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

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

  • RadiosurgeryRadiation

    Also called SRS

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

Study groups in NCT02978404
Study groupRoleWhat they receive
Radiosurgery and NivolumabExperimentalInterventions: 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.
Receives: Drug: Nivolumab; Radiation: Radiosurgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year

Secondary outcomes (11)

  1. Treated brain lesions control rate

    Treated brain lesions control will be assessed as per RECIST version 1.1.

    Measured: 1 year

  2. Overall survival after receiving Nivolumab.

    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.

    Measured: 2 years

  3. Maximum response rate of distant non-irradiated disease

    Response will be assessed as per RECIST version 1.1.

    Measured: 1 year

  4. Progression-free survival

    Response will be assessed as per RECIST version 1.1.

    Measured: 1 year

  5. Correlation between tumor PD-L1 expression and clinical outcomes

    Tumor PD-L1 expression level will be correlated with patient overall response rate, loco-regional recurrence free survival and overall survival.

    Measured: 1 year

  6. Patient quality of life

    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.

    Measured: 1 year

  7. Neurocognitive function, as measured by the HVLT-R

    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.

    Measured: 1 Year

  8. Neurocognitive function, as measured by TMT

    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.

    Measured: 1 year

  9. Neurocognitive function, as measured by COWA

    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.

    Measured: 1 Year

  10. Acute and late toxicity of SRS + Nivolumab

    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.

    Measured: 1 year

  11. Imaging indicators of response

    Patient response to the treatment will be analysed using the Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2016 (estimated)
  2. Study start2 Jun 2017
  3. Primary completion31 Jan 2021
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02978404
Sponsor's protocol ID
16.206
Other IDs
OZM-080
Status last verified
Jun 2024
First submitted
21 Nov 2016
Last updated
28 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Radiosurgery in people with Clear-Cell Metastatic Renal Cell Carcinoma and Non Small Cell Lung Cancer Metastatic, run by Centre hospitalier de l'Université de Montréal (CHUM) at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial progression-free survival (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02978404.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024.

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