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Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT

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ClinicalTrials.gov Identifier: NCT02962167
Recruitment Status : Recruiting
First Posted : November 11, 2016
Last Update Posted : December 4, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

This is a two 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).


Condition or disease Intervention/treatment Phase
Medulloblastoma, Childhood, Recurrent Atypical Teratoid/Rhabdoid Tumor Medulloblastoma Recurrent Biological: Modified Measles Virus Biological: Modified Measles Virus Lumbar Puncture Phase 1

Detailed Description:

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, MV-NIS will be directly administered into the tumor bed following a standard of care surgical resection. For patients with disseminated recurrence, MV-NIS will be injected via lumbar puncture (LP). This is a one-time administration for either locally or disseminated recurrence.

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : November 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : February 2019


Arms and Interventions

Arm Intervention/treatment
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.
Biological: Modified Measles Virus
Administration of MV-NIS either into the tumor bed, if surgery to remove local tumor
Other Name: MV-NIS
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).
Biological: Modified Measles Virus Lumbar Puncture
Administration of MV-NIS into the cerebrospinal fluid via lumbar puncture
Other Name: MV-NIS LP


Outcome Measures

Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Prior Therapy:

  • 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.

    • Biologic agent: Patient must have recovered from any 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.
  • 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.

    o 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.

    o 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 ≥12 weeks prior to registration
  • Had their last fraction of craniospinal irradiation or total body 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.

    • Anti-measles virus immunity as demonstrated by IgG anti-measles antibody per institutional guidelines (within 21 days prior to study registration).
    • Organ Function Requirements (within 7 days prior to study registration)
  • 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).

  • Adequate Renal Function Defined as:

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than or equal to 70mL/min/1.73 m2 or
    • A serum creatinine based on age/gender as follows:

Age

Maximum Serum

Creatinine (mg/dL)

Male Female

  1. - 2 years 0.6 0.6
  2. to < 6 years 0.8 0.8

6 to < 10 years 1 1

10 to < 13 years 1.2 1.2

13 to < 16 years 1.5 1.4

  • 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.

    • Adequate Liver Function Defined as:

      - Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age and

      - SGPT (ALT) less than or equal to 110 U/L. and

      - Serum albumin less than or equal to 2 g/dL.

      • The effects of MV-NIS on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of MV-NIS administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

      • Ability to understand and the willingness to sign a written informed consent document.

      -Exclusion Criteria

      -Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

      -Patients who are receiving any other investigational agents

      - History of allergic reactions attributed to compounds of similar chemical or biologic composition to measles virus vaccination

      -Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

      -Female patients of childbearing potential must not be pregnant or breast-feeding.

      -Female patients of childbearing potential must have a negative serum or urine pregnancy test (within 7 days prior to study registration)

      -HIV-positive patients

      • Patients with very low CD4 counts (<200/µL or 14% of total lymphocyte count)
      • Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
      • Exposure to household contact with known immunodeficiency
      • Allergy to measles vaccine or history of severe reaction to prior measles vaccination
      • History of chronic hepatitis B or C infection
      • History of organ transplantation
      • Patients with evidence of extraneural disease
      • Patients on chronic steroid use or other immunosuppressive agents
Contacts and Locations

Information from the National Library of Medicine

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): NCT02962167


Contacts
Contact: Sabine Mueller, MD, PhD, MAS (415) 476-3831 sabine.mueller@ucsf.edu
Contact: Lajhem Cambridge, MS (415) 502-1600 lajhem.cambridge@ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94158
Contact: Sabine Mueller, MD    415-476-3831    sabine.mueller@ucsf.edu   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Stewart Goldman, MD    312-227-4873    sgoldman@luriechildrens.org   
Contact: Rishi Lulla, MD    312-227-4874    rlulla@luriechildrens.org   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215-5450
Contact: Susan Chi, MD    617-632-4386    Susan_Chi@dfci.harvard.edu   
Contact: Daphne Haas-Kogan, MD    617-632-2291    Dhaas-kogan@lroc.harvard.edu   
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Karen Gauvain, MD    314-454-2002    gauvain_k@kids.wustl.edu   
Contact: Josh Rubin, MD    314-286-2790    rubin_j@kids.wustl.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jane Minturn, MD, PhD    267-426-5026    MINTURN@email.chop.edu   
Contact: Angela Waanders, MD    1-800-879-2467    waandersa@email.chop.edu   
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Sarah Leary, MD    206-987-2106    sarah.leary@seattlechildrens.org   
Contact: Nicholas Vitanza, MD    206-987-2106    nicholas.vitanza@seattlechildrens.org   
Sponsors and Collaborators
University of California, San Francisco
No More Kids With Cancer
The Matthew Larson Foundation for Pediatric Brain Tumors
Vyriad, Inc.
Mayo Clinic
Investigators
Study Chair: Sabine Mueller, MD, PhD, MAS University of California, San Francisco
More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02962167     History of Changes
Other Study ID Numbers: PNOC 005
150812 ( Other Identifier: University of California, San Francisco )
First Posted: November 11, 2016    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, San Francisco:
measles virus
recurrent medulloblastoma
recurrent ATRT

Additional relevant MeSH terms:
Medulloblastoma
Measles
Rhabdoid Tumor
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Morbillivirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Neoplasms, Complex and Mixed