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.
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.
Adults whose rare CNS tumor has returned.
Participants will be screened:
Heart and blood tests
Physical and neurological exam
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.
Participants will get nivolumab in a vein every 2 weeks for up to 64 weeks.
Participants 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 participants' tumor tissue. Participants will be contacted if
any clinically important results are found.
After treatment ends, participants 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
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
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.
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).
Documented recurrent or progressive disease that corresponds to one of the tumors
eligible for testing.
Age greater than or equal to 18 years of age.
Karnofsky Performance greater than or equal to 70%.
Tumor tissue available for central review to confirm morphologic diagnosis
Tumor tissue or slides available for central molecular and immune profiling
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.
Medulloblastoma, Ependymoma, Pineal Region Tumors, Choroid Plexus Tumors, Atypical/Malignant Meningioma
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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