Ignite Creation Date:
2025-12-25 @ 3:39 AM
Ignite Modification Date:
2025-12-26 @ 2:23 AM
Study NCT ID:
NCT06620302
Status:
RECRUITING
Last Update Posted:
2025-10-24
First Post:
2024-09-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma
Sponsor:
Children's Oncology Group
Organization:
Study Overview
Official Title:
DT2216 in Combination With Irinotecan for Children, Adolescents and Young Adults With Relapsed or Refractory Solid Tumors: A Phase I Study With Phase II Feasibility Cohort for Fibrolamellar Carcinoma
Status:
RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial tests the safety, side effects and best dose of DT2216 in combination with irinotecan and how well it works in treating children, adolescents and young adults with solid tumors and fibrolamellar cancer that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large targeted protein degrader. It may stop the growth of tumor cells by blocking Bcl-xL, a protein needed for tumor cell survival. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill tumor cells. Giving DT2216 in combination with irinotecan may be safe, tolerable, and/or effective in treating children, adolescents and young adults with relapsed or refractory solid tumors or fibrolamellar cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Bcl-xL proteolysis targeting chimera DT2216 (DT2216) in combination with intravenous irinotecan in patients with recurrent/refractory solid tumors.
II. To define and describe the toxicities of DT2216 in combination with irinotecan administered on this schedule in patients with recurrent/refractory solid tumors and patients with fibrolamellar carcinoma (FLC).
III. To characterize the pharmacokinetics of DT2216 in combination with irinotecan in patients with recurrent/refractory solid tumors and patients with fibrolamellar carcinoma (FLC).
IV. To preliminarily define antitumor activity of DT2216 in combination with irinotecan in patients with recurrent/refractory solid tumors (within the confines of a phase 1 study) and in patients with recurrent/refractory FLC.
SECONDARY OBJECTIVE:
I. To assess the pharmacodynamic activity of DT2216 in combination with irinotecan when administered intravenously in combination to children, adolescents, and young adults with recurrent/refractory cancer (solid tumors and FLC) by measuring peripheral mononuclear cell Bcl-xL levels and, where available, paired pre-treatment and on-(or recently off) treatment tumor samples using immunohistochemistry for TUNEL, Bcl-xL, Bcl2, Mcl1, and Ki67.
EXPLORATORY OBJECTIVES:
I. To explore the correlation of peripheral blood levels of the DNAJB1-PRKACA chimera, vitamin B12 levels and/or a panel of specific genomic markers, as well as intratumoral patterns of infiltrating immune cells as assessed by multiplex immunohistochemistry with disease characteristics of radiographic response in FLC patients.
II. To assess the ability of cross-sectional imaging to identify tumor involved pathological involved (positive) lymph nodes in FLC patients who undergo surgical resection including lymph node sampling or dissection.
OUTLINE: This is a phase I, dose-escalation study of DT2216 in combination with irinotecan, followed by a phase II study.
Patients receive DT2216 intravenously (IV) over 30 minutes on days 1, 4, 8, 11, 15, and 18 of each cycle and irinotecan IV over 90 minutes on days 2-6 of cycle 1, and on days 1-5 of remaining cycles. Cycles repeat every 21 days for up to 35 cycles (24 months) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the trial.
After completion of study treatment, patients are followed up every at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months.
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Bcl-xL proteolysis targeting chimera DT2216 (DT2216) in combination with intravenous irinotecan in patients with recurrent/refractory solid tumors.
II. To define and describe the toxicities of DT2216 in combination with irinotecan administered on this schedule in patients with recurrent/refractory solid tumors and patients with fibrolamellar carcinoma (FLC).
III. To characterize the pharmacokinetics of DT2216 in combination with irinotecan in patients with recurrent/refractory solid tumors and patients with fibrolamellar carcinoma (FLC).
IV. To preliminarily define antitumor activity of DT2216 in combination with irinotecan in patients with recurrent/refractory solid tumors (within the confines of a phase 1 study) and in patients with recurrent/refractory FLC.
SECONDARY OBJECTIVE:
I. To assess the pharmacodynamic activity of DT2216 in combination with irinotecan when administered intravenously in combination to children, adolescents, and young adults with recurrent/refractory cancer (solid tumors and FLC) by measuring peripheral mononuclear cell Bcl-xL levels and, where available, paired pre-treatment and on-(or recently off) treatment tumor samples using immunohistochemistry for TUNEL, Bcl-xL, Bcl2, Mcl1, and Ki67.
EXPLORATORY OBJECTIVES:
I. To explore the correlation of peripheral blood levels of the DNAJB1-PRKACA chimera, vitamin B12 levels and/or a panel of specific genomic markers, as well as intratumoral patterns of infiltrating immune cells as assessed by multiplex immunohistochemistry with disease characteristics of radiographic response in FLC patients.
II. To assess the ability of cross-sectional imaging to identify tumor involved pathological involved (positive) lymph nodes in FLC patients who undergo surgical resection including lymph node sampling or dissection.
OUTLINE: This is a phase I, dose-escalation study of DT2216 in combination with irinotecan, followed by a phase II study.
Patients receive DT2216 intravenously (IV) over 30 minutes on days 1, 4, 8, 11, 15, and 18 of each cycle and irinotecan IV over 90 minutes on days 2-6 of cycle 1, and on days 1-5 of remaining cycles. Cycles repeat every 21 days for up to 35 cycles (24 months) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the trial.
After completion of study treatment, patients are followed up every at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2024-06357 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| PEPN2411 | OTHER | Pediatric Early Phase Clinical Trial Network | View | |
| PEPN2411 | OTHER | CTEP | View | |
| UM1CA228823 | NIH | None | https://reporter.nih.gov/quic… | View |