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Trial record 18 of 77 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 : Not yet recruiting
First Posted : August 8, 2019
Last Update Posted : August 8, 2019
Sponsor:
Collaborator:
Emory University
Information provided by (Responsible Party):
Theodore S. Johnson, Augusta University

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.


Condition or disease Intervention/treatment Phase
Glioblastoma Medulloblastoma Ependymoma Diffuse Intrinsic Pontine Glioma Drug: Indoximod Radiation: Partial Radiation Radiation: Full-dose Radiation Drug: Temozolomide Drug: Cyclophosphamide Drug: Etoposide Drug: Lomustine Phase 2

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)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2026


Arm Intervention/treatment
Experimental: Core Regimen, sub-cohort A
For patients not eligible for re-irradiation; Start with Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
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.

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).
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).

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.

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).
Drug: Indoximod
Indoximod will be taken by mouth twice daily during radiation and until the first cycle of Core Regimen therapy.

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.

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).
Drug: Indoximod
Indoximod will be taken by mouth twice daily, throughout each chemo-immunotherapy 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.

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).
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: Lomustine
Lomustine will be taken by mouth once daily, on day 1 of each treatment cycle.




Primary Outcome Measures :
  1. 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.

  2. 12-month Overall Survival (OS) [ Time Frame: Up to 5 years ]
    For patients with newly diagnosed DIPG (diffuse intrinsic pontine glioma).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 5 years ]
  2. iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria) [ Time Frame: Up to 5 years ]
  3. Time to Regimen Failure (TTRF) [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


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): NCT04049669


Contacts
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Contact: Theodore S Johnson, MD, PhD 706-721-4962 thjohnson@augusta.edu
Contact: Robin Dobbins, RN 706-721-2154 RDOBBINS@augusta.edu

Locations
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United States, Georgia
Emory University, Children's Heathcare of Atlanta Not yet recruiting
Atlanta, Georgia, United States, 30342
Contact: Amy Autry-Bush    404-785-6011    amy.autry-bush@choa.org   
Principal Investigator: Tobey J MacDonald, MD         
Augusta University, Georgia Cancer Center Not yet recruiting
Augusta, Georgia, United States, 30912
Contact: Theodore S Johnson, MD, PhD    706-721-4962    thjohnson@augusta.edu   
Contact: Robin Dobbins, RN    706-721-2154    RDOBBINS@augusta.edu   
Principal Investigator: Theodore S Johnson, MD, PhD         
Sponsors and Collaborators
Theodore S. Johnson
Emory University
Investigators
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Principal Investigator: Theodore S Johnson, MD, PhD Augusta University

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Responsible Party: Theodore S. Johnson, Associate Professor, Augusta University
ClinicalTrials.gov Identifier: NCT04049669     History of Changes
Other Study ID Numbers: GCC1949
First Posted: August 8, 2019    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Theodore S. Johnson, Augusta University:
diffuse intrinsic pontine glioma
DIPG
IDO
indoleamine 2,3-dioxygenase
indoximod
pediatric
childhood
brain tumor
glioblastoma
medulloblastoma
ependymoma
radiation
temozolomide
cyclophosphamide
etoposide
lomustine
immunotherapy
immune
central nervous system
CNS
Additional relevant MeSH terms:
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Glioblastoma
Brain Neoplasms
Ependymoma
Medulloblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive
Cyclophosphamide
Temozolomide
Lomustine
Etoposide
Etoposide phosphate
Tryptophan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents