Childhood Fibrolamellar CarcinomaPhase 1/2NCT06620302
Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma
A Phase 1/2 study testing Bcl-XL Proteolysis Targeting Chimera DT2216, Biospecimen Collection and Irinotecan in people with Childhood Fibrolamellar Carcinoma and Recurrent Childhood Fibrolamellar Carcinoma, run by Children's Oncology Group at 21 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 39 years
- Conditions the study is for
- Childhood Fibrolamellar Carcinoma, Recurrent Childhood Fibrolamellar Carcinoma, Recurrent Childhood Malignant Solid Neoplasm
- What is being tested?
- Bcl-XL Proteolysis Targeting Chimera DT2216, Biospecimen Collection and Irinotecan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 21 sitesUnited States
- Study dates
- 12 Jun 2025to 30 Dec 2031
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 46Show fewer
- 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
- For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) ≥ 1000/µL
- For patients with solid tumors without known bone marrow involvement: Platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
- A creatinine based on age/gender as follows:
- 1 to < 2 years: Maximum serum creatinine (mg/dL) 0.6 (male), 0.6 (female)
- 2 to < 6 years: Maximum serum creatinine (mg/dL) 0.8 (male), 0.8 (female)
- 6 to < 10 years: Maximum serum creatinine (mg/dL) 1 (male), 1 (female)
- 10 to < 13 years: Maximum serum creatinine (mg/dL) 1.2 (male), 1.2 (female)
- 13 to < 16 years: Maximum serum creatinine (mg/dL) 1.5 (male), 1.4 (female)
- 16 to ≤ 39 years: Maximum serum creatinine (mg/dL) 1.7 (male), 1.4 (female)
- OR a 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2
- OR a glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard). Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
- Patients with solid tumors: Bilirubin (sum of conjugated + unconjugated or total) ≤ 1.5 x upper limit of normal (ULN) for age
- Patients with solid tumors: Alanine aminotransferase (ALT) ≤ 3 x ULN, unless attributed to tumor involvement then ALT ≤ 5 x ULN
- Note: For the purposes of this study the ULN for ALT is defined as 45 U/L
- Patients with solid tumors: Aspartate aminotransferase (AST) ≤ 3 x ULN, unless attributed to tumor involvement then AST ≤ 5 x ULN
- Note: For the purposes of this study the ULN for AST is defined as 50 U/L
- Patients with solid tumors: Albumin ≥ 2 g/dL
- Patients with solid tumors: International normalized ratio (INR) ≤ 2.5
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days. If needed, evaluate use of enzyme-inducing anticonvulsants
- Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior therapy must be ≤ grade 2, with the exception of decreased tendon reflex (DTR). Patient with any grade of tendon reflex decrease are eligible
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Hospital Los Angeles
Los Angeles, California, 90027
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Childhood Fibrolamellar Carcinoma, Recurrent Childhood Fibrolamellar Carcinoma, Recurrent Childhood Malignant Solid Neoplasm, Recurrent Fibrolamellar Carcinoma, Recurrent Malignant Solid Neoplasm, Refractory Childhood Fibrolamellar Carcinoma
- Being tested
- Bcl-XL Proteolysis Targeting Chimera DT2216, Biospecimen Collection, Irinotecan
- Medical subject headings
- Fibrolamellar hepatocellular carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bcl-XL Proteolysis Targeting Chimera DT2216Biological
Also called Antiapoptotic Protein Targeted Degrader DT2216, APTaD DT2216, Bcl-XL Degrader DT2216, Bcl-XL PROTAC DT2216
Given IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
IrinotecanDrug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (DT2216, irinotecan) | Experimental | Patients receive DT2216 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. Receives: Biological: Bcl-XL Proteolysis Targeting Chimera DT2216; Procedure: Biospecimen Collection; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AEs)
AEs will be assessed and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. A descriptive summary of all toxicities will be reported.
Measured: Up to 30 days after last dose of study drug
Dose-limiting toxicity (DLT)
AEs will be assessed and graded using NCI CTCAE v5.0. A descriptive summary of all toxicities will be reported.
Measured: Up to 21 days
Maximum tolerated dose (MTD)/ recommended phase 2 dose
MTD will be defined as the maximum dose at which fewer than one-third of patients experience DLT during cycle 1 of therapy.
Measured: Up to 21 days
Area under the dose concentration curve of DT2216
Median (minimum [min], maximum [max]) area under the dose concentration curve of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Clearance of DT2216
Median (min, max) clearance of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Half-life of DT2216
Median (min, max) Half-life of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Area under the dose concentration curve of irinotecan
Median (min, max) area under the dose concentration curve of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Clearance of irinotecan
Median (min, max) clearance of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Half-life of irinotecan
Median (min, max) Half-life of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Measured: Up to 7 hours
Overall response rate (ORR)
ORR will be recorded from the start of the treatment until disease progression or recurrence. ORR of partial response, complete response or stable disease will be assessed according to Response Evaluation Criteria in Solid Tumors Criteria and will be reported descriptively.
Measured: At start of treatment until disease progression or recurrence up to 60 months
Secondary outcomes (1)
Pharmacodynamic activity
Western blotting will be performed to assess the pharmacodynamic activity by measuring peripheral mononuclear cell Bcl-xL levels.
Measured: Up to end of cycle 5 (105 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start12 Jun 2025
- Primary completion30 Dec 2031 (estimated)
- Study completion30 Dec 2031 (estimated)
Why it stopped: Unacceptable Toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Fibrolamellar CarcinomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Michael V Ortiz, Principal investigator, Pediatric Early Phase Clinical Trial Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06620302
- Sponsor's protocol ID
- PEPN2411
- Other IDs
- NCI-2024-06357, PEPN2411, PEPN2411, UM1CA228823
- Status last verified
- Aug 2026
- First submitted
- 26 Sep 2024
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06620302
- Acronym / sponsor ID
- PEPN2411
- Conditions
- Childhood Fibrolamellar Carcinoma, Recurrent Childhood Fibrolamellar Carcinoma, Recurrent Childhood Malignant Solid Neoplasm, Recurrent Fibrolamellar Carcinoma, Recurrent Malignant Solid Neoplasm, Refractory Childhood Fibrolamellar Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Unacceptable Toxicity
- Enrolment
- 81 participants (estimated)
- Lead sponsor
- Children's Oncology GroupResearch network
- Study start
- 12 Jun 2025 (actual)
- Primary completion
- 30 Dec 2031 (estimated)
- Study completion
- 30 Dec 2031 (estimated)
- First posted
- 1 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (DT2216, irinotecan) | Experimental | Biological: Bcl-XL Proteolysis Targeting Chimera DT2216, Procedure: Biospecimen Collection, Drug: IrinotecanPatients receive DT2216 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. |
Who may qualify
- Ages
- 1 year to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (46 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bcl-XL Proteolysis Targeting Chimera DT2216Also: Antiapoptotic Protein Targeted Degrader DT2216, APTaD DT2216, Bcl-XL Degrader DT2216, Bcl-XL PROTAC DT2216Given IV | Biological | Treatment (DT2216, irinotecan) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (DT2216, irinotecan) |
| IrinotecanGiven IV | Drug | Treatment (DT2216, irinotecan) |
Primary outcome
Incidence of adverse events (AEs)
Time frame: Up to 30 days after last dose of study drug
AEs will be assessed and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. A descriptive summary of all toxicities will be reported.
Dose-limiting toxicity (DLT)
Time frame: Up to 21 days
AEs will be assessed and graded using NCI CTCAE v5.0. A descriptive summary of all toxicities will be reported.
Maximum tolerated dose (MTD)/ recommended phase 2 dose
Time frame: Up to 21 days
MTD will be defined as the maximum dose at which fewer than one-third of patients experience DLT during cycle 1 of therapy.
Area under the dose concentration curve of DT2216
Time frame: Up to 7 hours
Median (minimum [min], maximum [max]) area under the dose concentration curve of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Clearance of DT2216
Time frame: Up to 7 hours
Median (min, max) clearance of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Half-life of DT2216
Time frame: Up to 7 hours
Median (min, max) Half-life of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Area under the dose concentration curve of irinotecan
Time frame: Up to 7 hours
Median (min, max) area under the dose concentration curve of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Clearance of irinotecan
Time frame: Up to 7 hours
Median (min, max) clearance of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Half-life of irinotecan
Time frame: Up to 7 hours
Median (min, max) Half-life of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.
Overall response rate (ORR)
Time frame: At start of treatment until disease progression or recurrence up to 60 months
ORR will be recorded from the start of the treatment until disease progression or recurrence. ORR of partial response, complete response or stable disease will be assessed according to Response Evaluation Criteria in Solid Tumors Criteria and will be reported descriptively.
1 secondary outcome
Pharmacodynamic activity
Time frame: Up to end of cycle 5 (105 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
Related trials for Childhood Fibrolamellar Carcinoma
Active, not recruitingPhase 3
Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
Childhood Hepatocellular Carcinoma, Childhood Malignant Liver Neoplasm
RecruitingPhase 2
Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma
Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael V Ortiz principal investigator
Pediatric Early Phase Clinical Trial Network
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bcl-XL Proteolysis Targeting Chimera DT2216, Biospecimen Collection and Irinotecan in people with Childhood Fibrolamellar Carcinoma and Recurrent Childhood Fibrolamellar Carcinoma, run by Children's Oncology Group at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 46 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (AEs) (time frame: Up to 30 days after last dose of study drug). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.