November 2, 2016
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November 11, 2016
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March 20, 2024
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February 22, 2017
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May 10, 2023 (Final data collection date for primary outcome measure)
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- Number of Participants with Adverse Events as Assessed by CTCAE v5. [ Time Frame: 12 months ]
The safety of the modified measles virus will be assessed by monitoring for adverse events. Subjects will be monitored for adverse events via scheduled laboratory assessments, vital sign measurements, and physical examinations. The severity of any toxicity will be graded according to the NCI CTCAE v5.0. We will aggregate this information into the number of subjects with adverse events that are related to study treatment.
- Recommended Phase 2 Dose. [ Time Frame: 12 months ]
The maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) will be the dose level at which 6 evaluable patients have been treated and at most 1 patient experienced a dose limiting toxicity (DLT) and the next highest dose level is too toxic or we have reached the protocol defined highest dose level.
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- Number of Participants with Adverse Events as Assessed by CTCAE v4. [ Time Frame: 12 months ]
The safety of the modified measles virus will be assessed by monitoring for adverse events. Subjects will be monitored for adverse events via scheduled laboratory assessments, vital sign measurements, and physical examinations. The severity of any toxicity will be graded according to the NCI CTCAE v4.0. We will aggregate this information into the number of subjects with adverse events that are related to study treatment.
- Recommended Phase 2 Dose. [ Time Frame: 12 months ]
The maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) will be the dose level at which 6 evaluable patients have been treated and at most 1 patient experienced a DLT and the next highest dose level is too toxic or we have reached the protocol defined highest dose level.
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- Objective Response Rate (ORR) [ Time Frame: 24 months ]
Any eligible patient that receives MV-NIS will be considered evaluable for clinical efficacy. The objective response criteria is that partial response (PR) and complete response (CR) must be confirmed at least 8 weeks after the initial PR or CR criteria is met.
- Progression Free Survival (PFS) [ Time Frame: 24 months ]
For patients who are still progression free at the time of analysis, PFS will be censored at the last contact date. PFS will be estimated using the Kaplan-Meier method.
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Same as current
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The distribution of MV-NIS [ Time Frame: 12 months ] Subjects who consent to this optional study will receive an injection of technetium-99m (TC-99m) (pertechnetate) and then undergo SPECT imaging to determine MV-NIS distribution after local injection or after administration into the subarachnoid space.
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The distribution of MV-NIS [ Time Frame: 12 months ] Subjects who consent to this optional study will receive an injection of TC-99m (pertechnetate) and then undergo SPECT imaging to determine MV-NIS distribution after local injection or after administration into the subarachnoid space.
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Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT
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A Phase 1 Study of Modified Measles Virus (MV-NIS) for the Treatment of Children and Young Adults With Recurrent Medulloblastoma or Recurrent Atypical Teratoid Rhabdoid Tumors (ATRT)
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This is a three arm Phase I study within the Pacific Pediatric Neuro-Oncology Consortium (PNOC).
This study will look to determine the safety and recommended phase 2 dose of the modified measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma or atypical teratoid rhabdoid tumor (ATRT).
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This is an open label, multi-center, Phase I study to assess the safety of administering MV-NIS directly into the tumor bed (for locally recurrent medulloblastoma or ATRT patients) or into the subarachnoid space (for disseminated recurrent medulloblastoma or ATRT patients).
For locally recurrent patients (patients in the first arm) MV-NIS will be directly administered into the tumor bed following a standard of care surgical resection. For patients with disseminated recurrence (patients in the second or third arm), MV-NIS will be injected via lumbar puncture (LP).
Patients in the second arm will receive a one-time administration of MV-NIS. Patients will be closely monitored for 30 days after injection, and then followed for evaluation of 6 month progressive free survival and overall response rate.
Patients in the third arm will receive two administrations of MV-NIS. Patients will be closely monitored for 56 days after injection, and then followed for evaluation of 4 month progressive free survival.
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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Medulloblastoma, Childhood, Recurrent
- Atypical Teratoid/Rhabdoid Tumor
- Medulloblastoma Recurrent
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- Biological: Modified Measles Virus
Administration of MV-NIS either into the tumor bed, if surgery to remove local tumor
Other Name: MV-NIS
- Biological: Modified Measles Virus Lumbar Puncture
Administration of MV-NIS into the cerebrospinal fluid via lumbar puncture
Other Name: MV-NIS LP
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- Experimental: Locally Recurrent Medulloblastoma/ATRT
Patients must have local recurrent disease (defined as negative spine MRI and negative cytology within 21 days prior to study registration) and undergo resection of local recurrence as part of their standard of care. Patients must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy. Patients will receive the modified measles virus, MV-NIS, directly into the tumor bed during standard of care resection.
Intervention: Biological: Modified Measles Virus
- Experimental: Disseminated Recurrent MB/ATRT
Patients must have disseminated recurrent medulloblastoma (MB) or ATRT (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate CSF flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines. Patients must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy. Patients will receive the modified measles virus, MV-NIS, via lumbar puncture (modified measles virus lumbar puncture).
Intervention: Biological: Modified Measles Virus Lumbar Puncture
- Experimental: Disseminated Recurrent Medulloblastoma
Patients must have disseminated recurrent medulloblastoma (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate CSF flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines. Patients must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy. Patients will receive the modified measles virus, MV-NIS, via lumbar puncture (modified measles virus lumbar puncture).
Intervention: Biological: Modified Measles Virus Lumbar Puncture
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Not Provided
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Completed
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34
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24
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May 10, 2023
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May 10, 2023 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
• For stratum A, patients must have local recurrent disease (defined as negative spine MRI and negative cytology within 21 days prior to study registration) and undergo resection of local recurrence as part of their standard of care. Children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy.
- For stratum B, patients must have disseminated recurrent disease (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate cerebrospinal fluid (CSF) flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines. Children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy.
- For stratum C, patients must have disseminated recurrent disease (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate cerebrospinal fluid (CSF) flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines. Children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy.
Prior Therapy:
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The patient must have failed at least one prior therapy - surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy - prior to study registration. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
o Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks prior if nitrosourea.
o Biologic agent: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
- For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
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For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
- Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such patients should be discussed with the study chair prior to registration. For bevacizumab, patients must have received last dose ≥ 32 days prior to study registration.
- Bone Marrow Transplant: Patient must be:
- ≥ 6 months since allogeneic bone marrow transplant prior to registration
- ≥ 3 months since autologous bone marrow/stem cell prior to registration
- Radiation:
Patients must have:
- Had their last fraction of local irradiation to primary tumor ≥2 weeks prior to registration for local palliative radiation therapy (XRT) (small port)
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Had their last fraction of craniospinal irradiation ≥ 12 weeks prior to registration
• Age ≥ 12 months to less than or equal to 39 years of age
• Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age (See Appendix A). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Patients with pre-existing neurological deficits need to be stable prior to surgery or LP as determined by the investigator.
• Cluster of Differentiation 4 (CD4) (>= 200/microliter)
• Organ Function Requirements (within 7 days prior to study registration)
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Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and
- Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
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Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than or equal to 70 milliliters (mL)/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
Maximum Serum/Creatinine (mg/dL)
Age Male Female
- - 2 years 0.6 0.6
- to <6 years 0.8 0.8
6 to <10 years 1 1
10 to <13 years1.2 1.2
13 to <16 years1.5 1.4
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Sexes Eligible for Study: |
All |
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12 Months to 39 Years (Child, Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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NCT02962167
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PNOC 005 150812 ( Other Identifier: University of California, San Francisco ) NCI-2017-01831 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Sabine Mueller, MD, PhD, University of California, San Francisco
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University of California, San Francisco
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Sabine Mueller, MD, PhD
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University of California, San Francisco
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- No More Kids With Cancer
- The Matthew Larson Foundation for Pediatric Brain Tumors
- Vyriad, Inc.
- Mayo Clinic
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Study Chair: |
Sabine Mueller, MD, PhD, MAS |
University of California, San Francisco |
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University of California, San Francisco
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March 2024
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