Ignite Creation Date:
2024-10-25 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06620302
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-26
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:
None
Organization:
None
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:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
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 III 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 DNA repair and may kill tumor cells Giving DT2216 in combination with irinotecan may be safe tolerable andor 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 andor recommended phase 2 dose RP2D of BCL-XL proteolysis targeting chimera DT2216 DT2216 in combination with intravenous irinotecan in patients with recurrentrefractory solid tumors
II To define and describe the toxicities of DT2216 in combination with irinotecan administered on this schedule in patients with recurrentrefractory solid tumors and patients with fibrolamellar carcinoma FLC
III To characterize the pharmacokinetics of DT2216 in combination with irinotecan in patients with recurrentrefractory solid tumors and patients with fibrolamellar carcinoma FLC
IV To define antitumor activity of DT2216 in combination with irinotecan in patients with recurrentrefractory solid tumors within the confines of a phase 1 study and in patients with recurrentrefractory 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 recurrentrefractory cancer solid tumor 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 andor 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 andor recommended phase 2 dose RP2D of BCL-XL proteolysis targeting chimera DT2216 DT2216 in combination with intravenous irinotecan in patients with recurrentrefractory solid tumors
II To define and describe the toxicities of DT2216 in combination with irinotecan administered on this schedule in patients with recurrentrefractory solid tumors and patients with fibrolamellar carcinoma FLC
III To characterize the pharmacokinetics of DT2216 in combination with irinotecan in patients with recurrentrefractory solid tumors and patients with fibrolamellar carcinoma FLC
IV To define antitumor activity of DT2216 in combination with irinotecan in patients with recurrentrefractory solid tumors within the confines of a phase 1 study and in patients with recurrentrefractory 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 recurrentrefractory cancer solid tumor 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 andor 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:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None