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

Recruiting now · Phase 1/Phase 2

Conditions studied: Childhood Fibrolamellar Carcinoma, Recurrent Childhood Fibrolamellar Carcinoma, Recurrent Childhood Malignant Solid Neoplasm, Recurrent Fibrolamellar Carcinoma, Recurrent Malignant Solid Neoplasm, Refractory Childhood Fibrolamellar Carcinoma, Refractory Childhood Malignant Solid Neoplasm, Refractory Fibrolamellar Carcinoma, Refractory Malignant Solid Neoplasm

In brief

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.

Key facts

Study ID

NCT06620302

Run by

Children's Oncology Group

People needed

81

Starts

2025-06-12

Expected to finish

2031-12-30

Last updated by the study team

2026-05-05

Who can join

Age: 1 and older, up to 39. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Patients with FLC that is unresectable at initial diagnosis but is not recurrent/refractory to at least one prior line of systemic therapy nor metastatic are NOT eligible for either phase 1 or phase 2
• 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]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: ≥ 30 days
• Cellular therapy: ≥ 30 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiotherapy (XRT)/external beam irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (eg, radiolabeled antibody, lobenguane I-131 [131I-MIBG]): ≥ 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior Bcl-xL specific therapy (e.g. navitoclax, DT2216). Prior therapy with irinotecan or other topoisomerase 1 inhibitors and/or other BH3 mimetics which are not Bcl-xL selective (e.g. venetoclax) are acceptable

You may not qualify if…

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Patients who could become pregnant should use highly effective contraception during therapy and for 6 months after the last irinotecan dose or 120 days after the last dose of DT2216, whichever is longer. Patients with partners who could become pregnant should use condoms during therapy and for 3 months after the last dose irinotecan or 120 days after the last dose of DT2216, whichever is longer
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment are not eligible
• Patients with lymphoma are excluded
• Patients who have an uncontrolled infection are not eligible
• Patients with grade ≥ 2 diarrhea at baseline are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Dedicated central nervous system (CNS) imaging is not required but patients with current active CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, are not eligible
• Patients with grade > 2 corrected QT interval (i.e. electrocardiogram [EKG] showing corrected QT interval [QTc] > 480 ms) at baseline are not eligible
• Surgical procedure
• Central line placement, open or core needle biopsy of sites other than liver: < 2 days prior to enrollment.
• Open or laparoscopic biopsies or core needle biopsies of liver < 7 days prior to enrollment.
• All other surgeries < 14 days prior to enrollment

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States (enrolling)
• Children's Hospital Los Angeles — Los Angeles, California, United States (enrolling)
• Children's Hospital of Orange County — Orange, California, United States (enrolling)
• UCSF Medical Center-Mission Bay — San Francisco, California, United States (enrolling)
• Children's Hospital Colorado — Aurora, Colorado, United States (enrolling)
• Children's National Medical Center — Washington D.C., District of Columbia, United States (enrolling)
• Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States (enrolling)
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States (enrolling)
• Riley Hospital for Children — Indianapolis, Indiana, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States (enrolling)
• University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States (enrolling)
• Washington University School of Medicine — St Louis, Missouri, United States (enrolling)
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (enrolling)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States (enrolling)
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States (enrolling)
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States (enrolling)
• Seattle Children's Hospital — Seattle, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

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