Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer
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|ClinicalTrials.gov Identifier: NCT05106296|
Recruitment Status : Recruiting
First Posted : November 3, 2021
Last Update Posted : April 1, 2022
Recent lab-based discoveries suggest that IDO (indoleamine 2,3-dioxygenase) and BTK (Bruton's tyrosine Kinase) form a closely linked metabolic checkpoint in tumor-associated antigen-presenting cells. The central clinical hypothesis for the GCC2020 study is that combining ibrutinib (BTK-inhibitor) with indoximod (IDO-inhibitor) during chemotherapy will synergistically enhance anti-tumor immune responses, leading to improvement in clinical response with manageable overlapping toxicity.
GCC2020 is a prospective open-label phase 1 trial to determine the best safe dose of ibrutinib to use in combination with a previously studied chemo-immunotherapy regimen, comprised of the IDO-inhibitor indoximod plus oral metronomic cyclophosphamide and etoposide (4-drug combination) for participants, age 12 to 25 years, with relapsed or refractory ependymoma, medulloblastoma/PNET, or glioblastoma that progressed after previous treatment with indoximod plus temozolomide. Those previously treated with indoximod plus temozolomide are eligible, including prior treatment via the on-going phase 2 indoximod study (GCC1949, NCT04049669), the now closed phase 1 study (NLG2105, NCT02502708), or expanded access protocols. A dose-escalation cohort will determine the best safe dose of ibrutinib for the 4-drug combination. This will be followed by an expansion cohort, using ibrutinib at the best safe dose in the 4-drug combination, to allow assessment of preliminary evidence of efficacy.
|Condition or disease||Intervention/treatment||Phase|
|Ependymoma Medulloblastoma Glioblastoma Primitive Neuroectodermal Tumor (PNET)||Drug: Ibrutinib Drug: Indoximod Drug: Cyclophosphamide Drug: Etoposide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Repurposing Ibrutinib for Chemo-Immunotherapy in a Phase 1b Study of Ibrutinib With Indoximod Plus Metronomic Cyclophosphamide and Etoposide for Pediatric Patients With Brain Cancer|
|Actual Study Start Date :||February 8, 2022|
|Estimated Primary Completion Date :||March 2025|
|Estimated Study Completion Date :||April 2025|
Experimental: Treatment Regimen
Patients will be treated with the 4-drug chemo-immunotherapy regimen. Cycles are a minimum of 28 days, and maximum treatment duration is 12 cycles.
Ibrutinib will be taken by mouth once daily, on days 1-21 of each treatment cycle.
Indoximod will be taken by mouth twice daily, throughout each treatment cycle.
Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
Etoposide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
- Incidence of regimen-limiting toxicity (RLT) [ Time Frame: First 90 days of treatment ]To determine the pediatric recommended phase 2 dose (RP2D) of ibrutinib, when combined with indoximod-based chemo-immunotherapy (4-drug combination therapy)
- Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]Defined as the proportion of patients with a best objective response of either complete response (CR) or partial response (PR) to evaluate preliminary evidence of efficacy of ibrutinib, when combined with indoximod-based chemo-immunotherapy (4-drug combination therapy), using "immunotherapy Response Assessment for Neuro-Oncology" (iRANO) criteria
- Adverse events (AEs) [ Time Frame: Up to 13 months ]To assess frequency, severity, and recoverability of AEs for the treatment regimen
- Frequency of cycle delays for toxicity [ Time Frame: Up to 12 months ]To assess whether the immunotherapy contributes to delays in starting subsequent cycles of the chemotherapy drugs
- Frequency of dose-reductions of the chemotherapy regimen [ Time Frame: Up to 12 months ]To assess whether the immunotherapy contributes to reductions in the doses of the chemotherapy drugs
- Complete Response Rate (CRR) [ Time Frame: Up to 5 years ]Defined as the proportion of patients with a best objective response of CR using iRANO criteria
- Partial Response Rate (PRR) [ Time Frame: Up to 5 years ]Defined as the proportion of patients with a best objective response of PR using iRANO criteria
- Modified Objective Response Rate (mORR) [ Time Frame: Up to 5 years ]Defined as the proportion of patients with best objective response of complete response (CR), partial response (PR), or stable disease (SD, on at least 2 sequential study-timed MRIs) using iRANO criteria
- iRANO-PFS [ Time Frame: Up to 5 years ]Time of Progression-Free Survival (PFS), defined as time from study entry to progression using iRANO criteria
- Overall Survival (OS) [ Time Frame: Up to 5 years ]Time from study entry to death
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): NCT05106296
|Contact: Theodore S. Johnson, MD, PhDemail@example.com|
|Contact: Taylor King, RN||706-721-2949||TAYKING@AUGUSTA.EDU|
|United States, Georgia|
|Augusta University, Georgia Cancer Center||Recruiting|
|Augusta, Georgia, United States, 30912|
|Contact: Theodore S Johnson, MD, PhD 706-721-4962 firstname.lastname@example.org|
|Contact: Taylor King, RN 706-721-2949 TAYKING@AUGUSTA.EDU|
|Principal Investigator: Theodore S Johnson, MD, PhD|
|Principal Investigator:||Theodore S. Johnson, MD, PhD||Augusta University|