Ignite Creation Date:
2025-12-24 @ 4:54 PM
Ignite Modification Date:
2026-01-13 @ 5:08 AM
Study NCT ID:
NCT03173950
Status:
COMPLETED
Last Update Posted:
2025-06-29
First Post:
2017-05-31
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase II Trial of the Immune Checkpoint Inhibitor Nivolumab in Patients With Recurrent Select Rare CNS Cancers
Status:
COMPLETED
Status Verified Date:
2025-06-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors.
Objectives:
To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.
Eligibility:
Adults whose rare CNS tumor has returned.
Design:
Individuals will be screened:
* Heart and blood tests
* Physical and neurological exam
* Hepatitis tests
* Pregnancy test
* MRI. They will lay in a machine that takes pictures.
* Tumor tissue sample. This can be from a previous procedure.
At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.
Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks.
Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.
Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found.
After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....
More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors.
Objectives:
To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.
Eligibility:
Adults whose rare CNS tumor has returned.
Design:
Individuals will be screened:
* Heart and blood tests
* Physical and neurological exam
* Hepatitis tests
* Pregnancy test
* MRI. They will lay in a machine that takes pictures.
* Tumor tissue sample. This can be from a previous procedure.
At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.
Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks.
Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.
Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found.
After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....
Detailed Description:
Background:
* There are more than 130 identified primary tumors of the central nervous system (CNS). Most have an annual incidence of less than 1000 in the United States.
* Given the rarity of each of the tumors listed above, there is a paucity of proven therapies. Most of these neoplasms are treated with maximum surgical resection followed by treatment with external beam radiotherapy. With few exceptions (medulloblastoma, adult ependymoma), there are no effective systemic regimens and even in chemotherapy sensitive disease, most patients with recurrence eventually have no remaining salvage treatments available.
* In the setting of this unmet need, we propose to create a basket protocol that will evaluate the efficacy of the PD-1 inhibitor, nivolumab, in patients with refractory rare central nervous system neoplasms.
* This study seeks to establish effective therapies at recurrence in patients with rare CNS tumors. We hypothesize that this therapy will improve progression free survival and/or objective responses.
* It will be important to determine whether any determined survival benefit is associated with improvements in symptoms or does a worsening of symptoms offset the increase in survival. Precedence exists for measuring non-therapeutic endpoints in oncology research, and specifically in studies evaluating therapeutic benefit in patients with CNS tumors. There have been efforts in neuro-oncology to evaluate secondary endpoints using validated instruments as an additional indicator of benefit. The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Spine Tumor Module (MDASI-SP) allow for the self-reporting of symptom severity and interference with daily activities for patients with either brain or spinal cord tumors. The availability of validated instruments provides an opportunity to prospectively assess the impact of treatment, both positive and negative, on patients.
Objective:
Determine the efficacy of nivolumab in a variety of recurrent, refractory primary central nervous system tumors as measured by disease control rate (confirmed CR/PR or durable SD for at least 6 months).
Eligibility:
* Documented recurrent or progressive disease that corresponds to one of the tumors eligible for testing.
* Age \>= 18 years of age.
* Karnofsky Performance \>= 70%.
* Tumor tissue available for central review to confirm morphologic diagnosis
* Tumor tissue or slides must be available for central molecular and immune profiling.
Design:
* This is an open label phase II clinical trial. Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks (+/- 3 days) for cycles 1 through 2, then doses of 480 mg every 4 weeks (+/- 3 days) for a total of 14 additional doses (cycles). A maximum of 18 treatments will be given (64 weeks).
* A cycle will be defined as 4 weeks and patients will undergo efficacy assessments using MR imaging (and/or other imaging tests if applicable) every 2 cycles. Toxicity assessments will occur before the initiation of each cycle and patient outcomes measures (PROs) will be completed at the time of each imaging study (every 2 cycles) but prior to the patient being informed of the imaging results.
* After completion of the planned treatment course or if treatment was stopped because of toxicity, patients will undergo imaging evaluations and PRO measurements every 8 weeks (or 2 months) for one year, then every 3 months for the next year, then every 4
months for the next year and then every 6 months while the patient remains on the protocol. Patients off treatment because of disease progression will not undergo future imaging or PRO assessments on this protocol.
* Bayesian Optimal Phase 2 design (BOP2), will be used to conduct this phase II trial in patients with a variety of recurrent, refractory primary central nervous system tumors.
* The study will be comprised of 2 disease cohorts: heavily pretreated (defined as having received 3 or more prior therapies) and non-heavily pretreated (defined as having received up to 2 prior therapies). Each cohort will be evaluated independently for efficacy.
* There are more than 130 identified primary tumors of the central nervous system (CNS). Most have an annual incidence of less than 1000 in the United States.
* Given the rarity of each of the tumors listed above, there is a paucity of proven therapies. Most of these neoplasms are treated with maximum surgical resection followed by treatment with external beam radiotherapy. With few exceptions (medulloblastoma, adult ependymoma), there are no effective systemic regimens and even in chemotherapy sensitive disease, most patients with recurrence eventually have no remaining salvage treatments available.
* In the setting of this unmet need, we propose to create a basket protocol that will evaluate the efficacy of the PD-1 inhibitor, nivolumab, in patients with refractory rare central nervous system neoplasms.
* This study seeks to establish effective therapies at recurrence in patients with rare CNS tumors. We hypothesize that this therapy will improve progression free survival and/or objective responses.
* It will be important to determine whether any determined survival benefit is associated with improvements in symptoms or does a worsening of symptoms offset the increase in survival. Precedence exists for measuring non-therapeutic endpoints in oncology research, and specifically in studies evaluating therapeutic benefit in patients with CNS tumors. There have been efforts in neuro-oncology to evaluate secondary endpoints using validated instruments as an additional indicator of benefit. The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Spine Tumor Module (MDASI-SP) allow for the self-reporting of symptom severity and interference with daily activities for patients with either brain or spinal cord tumors. The availability of validated instruments provides an opportunity to prospectively assess the impact of treatment, both positive and negative, on patients.
Objective:
Determine the efficacy of nivolumab in a variety of recurrent, refractory primary central nervous system tumors as measured by disease control rate (confirmed CR/PR or durable SD for at least 6 months).
Eligibility:
* Documented recurrent or progressive disease that corresponds to one of the tumors eligible for testing.
* Age \>= 18 years of age.
* Karnofsky Performance \>= 70%.
* Tumor tissue available for central review to confirm morphologic diagnosis
* Tumor tissue or slides must be available for central molecular and immune profiling.
Design:
* This is an open label phase II clinical trial. Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks (+/- 3 days) for cycles 1 through 2, then doses of 480 mg every 4 weeks (+/- 3 days) for a total of 14 additional doses (cycles). A maximum of 18 treatments will be given (64 weeks).
* A cycle will be defined as 4 weeks and patients will undergo efficacy assessments using MR imaging (and/or other imaging tests if applicable) every 2 cycles. Toxicity assessments will occur before the initiation of each cycle and patient outcomes measures (PROs) will be completed at the time of each imaging study (every 2 cycles) but prior to the patient being informed of the imaging results.
* After completion of the planned treatment course or if treatment was stopped because of toxicity, patients will undergo imaging evaluations and PRO measurements every 8 weeks (or 2 months) for one year, then every 3 months for the next year, then every 4
months for the next year and then every 6 months while the patient remains on the protocol. Patients off treatment because of disease progression will not undergo future imaging or PRO assessments on this protocol.
* Bayesian Optimal Phase 2 design (BOP2), will be used to conduct this phase II trial in patients with a variety of recurrent, refractory primary central nervous system tumors.
* The study will be comprised of 2 disease cohorts: heavily pretreated (defined as having received 3 or more prior therapies) and non-heavily pretreated (defined as having received up to 2 prior therapies). Each cohort will be evaluated independently for efficacy.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 17-C-0102 | None | None | View |