Loading clinical trials...

Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma

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

NCT06620302•Children's Oncology Group

View on ClinicalTrials.gov

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.

Eligibility

Age

1 - 39 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•PHASE 1: Patients between ≥ 1 year and ≤ 21 years of age at the time of study enrollment
•PHASE 2: Patients between ≥ 1 year and ≤ 39 years of age at the time of study enrollment
•PHASE 1: Patients with recurrent/refractory solid tumors excluding primary central nervous system tumors
•PHASE 2: Patients with (FLC), which must include genomic confirmation of the DNAJB1:PRKACA fusion performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
•PHASE 1: Patients must have either measurable or evaluable disease
•PHASE 2: Patients must have measurable disease
•PHASE 1: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
•PHASE 2: Patients must have FLC which is recurrent/refractory to at least one line of prior systemic therapy

Exclusion Criteria

•Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
•Patients must have fully recovered (grade \< 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, eg, blood count criteria, the patient is considered to have recovered adequately
•* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
•* Solid tumor patients: ≥ 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/anticancer agents on the COG website
•* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
•* Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
•* Corticosteroids: If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
•* Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (eg, pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
•* Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
•* Stem cell Infusions (with or without total body irradiation \[TBI\]):
+33 more criteria

Locations (20)

Children's Hospital of Alabama

Birmingham, Alabama, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Key Dates

Start Date

June 12, 2025

Primary Completion Date

December 30, 2031

Completion Date

December 30, 2031

Last Updated

February 24, 2026

Enrollment

ESTIMATED participants

Conditions

Childhood Fibrolamellar CarcinomaRecurrent Childhood Fibrolamellar CarcinomaRecurrent Childhood Malignant Solid NeoplasmRecurrent Fibrolamellar CarcinomaRecurrent Malignant Solid NeoplasmRefractory Childhood Fibrolamellar CarcinomaRefractory Childhood Malignant Solid NeoplasmRefractory Fibrolamellar CarcinomaRefractory Malignant Solid Neoplasm

Interventions

Bcl-XL Proteolysis Targeting Chimera DT2216

BIOLOGICAL

Biospecimen Collection

PROCEDURE

Irinotecan

DRUG