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Trial record 18 of 78 for:    DIPG

Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG

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ClinicalTrials.gov Identifier: NCT04049669
Recruitment Status : Recruiting
First Posted : August 8, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborators:
Emory University
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Theodore S. Johnson, Augusta University

Tracking Information
First Submitted Date  ICMJE August 2, 2019
First Posted Date  ICMJE August 8, 2019
Last Update Posted Date October 4, 2019
Actual Study Start Date  ICMJE October 2, 2019
Estimated Primary Completion Date October 2, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • 8-month iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria) [ Time Frame: Up to 5 years ]
    For patients with relapsed glioblastoma, medulloblastoma, or ependymoma.
  • 12-month Overall Survival (OS) [ Time Frame: Up to 5 years ]
    For patients with newly diagnosed DIPG (diffuse intrinsic pontine glioma).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04049669 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
  • iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria) [ Time Frame: Up to 5 years ]
  • Time to Regimen Failure (TTRF) [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Official Title  ICMJE Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG
Brief Summary

Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and thereby slow the growth of tumors.

The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent approach for breaking immune tolerance to pediatric tumors that will improve outcomes, relative to standard therapy alone.

This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial using indoximod-based combination chemo-radio-immunotherapy for treatment of patients age 3 to 21 years who have progressive brain cancer (glioblastoma, medulloblastoma, or ependymoma), or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical analysis will stratify patients based on whether their treatment plan includes up-front radiation (or proton) therapy in combination with indoximod. Central review of tissue diagnosis from prior surgery is required, except non-biopsied DIPG. This study will use the "immune-adapted Response Assessment for Neuro-Oncology" (iRANO) criteria for measurement of outcomes. Planned enrollment is up to 140 patients.

Detailed Description

Disease-specific Cohorts :

Cohort 1A, 1B: progressive glioblastoma (relapsed or refractory)

Cohort 2A, 2B: progressive medulloblastoma (relapsed or refractory)

Cohort 3A, 3B, 3C: progressive ependymoma (relapsed or refractory)

Cohort 4C: newly-diagnosed DIPG (must have no prior radiation or other therapy)

.

Radiation (or proton) plan sub-cohorts:

Sub-cohort A: for patients not eligible for re-irradiation

Sub-cohort B: for patients who are eligible for partial re-irradiation

Sub-cohort C: for patients who are eligible for full-dose radiation (All newly diagnosed DIPG patients and some relapsed ependymoma patients)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Medulloblastoma
  • Ependymoma
  • Diffuse Intrinsic Pontine Glioma
Intervention  ICMJE
  • Drug: Indoximod
    Indoximod will be taken by mouth twice daily during radiation and until the first cycle of Core Regimen therapy.
  • Radiation: Partial Radiation
    Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).
  • Radiation: Full-dose Radiation
    Palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine).
  • Drug: Indoximod
    Indoximod will be taken by mouth twice daily, throughout each chemo-immunotherapy treatment cycle.
  • Drug: Temozolomide
    Temozolomide will be taken by mouth once daily, on days 1-5 of each treatment cycle.
  • Drug: Cyclophosphamide
    Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
  • Drug: Etoposide
    Etoposide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
  • Drug: Lomustine
    Lomustine will be taken by mouth once daily, on day 1 of each treatment cycle.
Study Arms  ICMJE
  • Experimental: Core Regimen, sub-cohort A
    For patients not eligible for re-irradiation; Start with Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
    Interventions:
    • Drug: Indoximod
    • Drug: Temozolomide
  • Experimental: Core Regimen, sub-cohort B
    For patients who are eligible for partial re-irradiation; Start with indoximod plus up-front re-irradiation, using a palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
    Interventions:
    • Drug: Indoximod
    • Radiation: Partial Radiation
    • Drug: Indoximod
    • Drug: Temozolomide
  • Experimental: Core Regimen, sub-cohort C
    For patients who are eligible for full-dose radiation; (All newly diagnosed DIPG patients and some relapsed ependymoma patients); Start with indoximod plus up-front radiation, using a palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
    Interventions:
    • Drug: Indoximod
    • Radiation: Full-dose Radiation
    • Drug: Indoximod
    • Drug: Temozolomide
  • Experimental: Salvage Regimen 1
    For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral metronomic cyclophosphamide and etoposide).
    Interventions:
    • Drug: Indoximod
    • Drug: Cyclophosphamide
    • Drug: Etoposide
  • Experimental: Salvage Regimen 2
    For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral lomustine and temozolomide).
    Interventions:
    • Drug: Indoximod
    • Drug: Temozolomide
    • Drug: Lomustine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2019)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2, 2026
Estimated Primary Completion Date October 2, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Diagnosis:

  • Progressive disease with histologically proven initial diagnosis of glioblastoma, medulloblastoma, or ependymoma; With confirmation of progression by either MRI or CSF analysis; Measureable disease is not required for study entry; Patients with progressive disease must have been previously treated with therapeutic radiation as part of treatment for the initial brain cancer diagnosis or for a prior relapse.
  • Newly diagnosed DIPG (diffuse intrinsic pontine glioma) with no prior therapy (including no prior radiation); Biopsy is not required for DIPG.
  • Central review of tissue diagnosis is required, except non-biopsied DIPG; Archival tumor tissue must be located and available prior to study entry.
  • Patients with metastatic disease are eligible.

Lansky or Karnofsky performance status score must be ≥ 50%.

Adequate renal function: creatinine ≤ 1.5-times upper limit of age-adjusted normal.

Adequate liver function:

  • ALT ≤ 5-times upper limit of normal.
  • Total bilirubin ≤ 1.5-times upper limit of normal.

Adequate Bone marrow function:

  • Absolute neutrophil count (ANC) ≥ 750/mcL.
  • Platelets ≥ 75,000/mcL (transfusion independent).
  • Hemoglobin ≥ 8 g/dL (transfusion independent).

Central nervous system: seizure disorders must be well controlled on antiepileptic medication.

Prior therapy

  • DIPG patients must not have been treated with any prior radiation or medical therapy.
  • Patients previously treated with indoximod are excluded.
  • Patients previously treated with any other immunotherapy agent, including other IDO-targeted drugs, are eligible for enrollment.
  • Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.

Patients must be 14 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:

  • Temozolomide dosed at or above 150 mg/m2 (allowed, but must be at least 21 days from the last dose of temozolomide).
  • Must be 28 days from administration of antibody-based therapies (e.g., bevacizumab), tumor-directed vaccines, or cellular immune therapies (e.g., T cells, NK cells, etc).
  • Must be 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc).

Pregnant women are excluded from this study, where pregnancy is confirmed by a positive urine or serum hCG laboratory test.

Patients must be able to swallow pills.

.

Exclusion Criteria:

Patients who cannot swallow indoximod pills are excluded.

Patients previously treated with indoximod are excluded.

Patients with DIPG who have been treated with any prior radiation or medical therapy are excluded.

Midline glioma that does not include significant brain stem involvement is not considered DIPG for enrollment purposes, and is excluded.

Patients with active systemic infection requiring treatment, including any HIV infection or toxoplasmosis, are excluded.

Patients with active autoimmune disease that requires systemic therapy are excluded.

Pregnant women are excluded

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Theodore S Johnson, MD, PhD 706-721-4962 thjohnson@augusta.edu
Contact: Robin Dobbins, RN 706-721-2154 RDOBBINS@augusta.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04049669
Other Study ID Numbers  ICMJE GCC1949
R01CA229646 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Theodore S. Johnson, Augusta University
Study Sponsor  ICMJE Theodore S. Johnson
Collaborators  ICMJE
  • Emory University
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Theodore S Johnson, MD, PhD Augusta University
PRS Account Augusta University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP