Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
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ClinicalTrials.gov Identifier: NCT04851119 |
Recruitment Status :
Recruiting
First Posted : April 20, 2021
Last Update Posted : April 22, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | April 12, 2021 | ||||
First Posted Date ICMJE | April 20, 2021 | ||||
Last Update Posted Date | April 22, 2024 | ||||
Actual Study Start Date ICMJE | November 8, 2021 | ||||
Estimated Primary Completion Date | June 30, 2028 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
Antitumor effects of tegavivint in patients with solid tumors [ Time Frame: Up to 336 days ] Frequency (%) of solid tumor patients with at least partial response to tegavivint at the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) stratified by study part and disease cohort.
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Original Secondary Outcome Measures ICMJE |
Antitumor effects of tegavivint in patients with solid tumors [ Time Frame: Up to 12 cycles (1 cycle = 28 days) ] Frequency of solid tumor patients with at least partial response to tegavivint at the MTD/RP2D.
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors | ||||
Official Title ICMJE | A Phase 1/2 Study of Tegavivint (NSC#826393) in Children, Adolescents, and Young Adults With Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors | ||||
Brief Summary | This phase I/II trial evaluates the highest safe dose, side effects, and possible benefits of tegavivint in treating patients with solid tumors that has come back (recurrent) or does not respond to treatment (refractory). Tegavivint interferes with the binding of beta-catenin to TBL1, which may help stop the growth of tumor cells by blocking the signals passed from one molecule to another inside a cell that tell a cell to grow. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of tegavivint administered as an intravenous (IV) infusion over 4 hours, once weekly for 3 weeks, followed by a 1 week rest, in a 28-day cycle to pediatric patients with recurrent/refractory solid tumors, including non-Hodgkin lymphoma and desmoid tumors. (Phase 1 Dose Escalation) II. To preliminarily define antitumor activity of tegavivint in pediatric patients with recurrent or refractory Ewing sarcoma, liver tumors (hepatocellular carcinoma [HCC] and hepatoblastoma), osteosarcoma, Wilms tumor, desmoid tumors, and tumors with Wnt pathway aberrations. (Phase 2) III. To define and describe the toxicities of tegavivint administered on this schedule. (Phase I) IV. To characterize the pharmacokinetics of tegavivint in pediatric patients with recurrent or refractory cancer. (Phase I) SECONDARY OBJECTIVE: I. To preliminarily define the antitumor activity of tegavivint for pediatric patients with recurrent/refractory solid tumors, including lymphoma and desmoid tumors within the confines of a Phase 1 study. EXPLORATORY OBJECTIVES: I. To test whether baseline activity of the WNT/beta catenin pathway correlates with clinical response using archived tumor tissue. II. To characterize pharmacodynamic changes in tumor tissue to examine target engagement by tegavivint. III. To characterize pharmacodynamic activity of tegavivint on serum protein biomarkers. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive tegavivint IV over 4 hours on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 26 cycles or 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray at baseline, after cycle 1, and then every 3 cycles while on treatment and a dual x-ray absorptiometry (DEXA) scan at baseline, every 6 cycles while on treatment, at months 12 and 24, and then annually up to 60 months following end of therapy. Patients may also undergo blood sample collection throughout the trial. After completion of study intervention, patients are followed up every 3 months for 12 months, every 6 months for 24 months, and then annually for 60 months. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (tegavivint)
Tegavivint will be administered IV over 4 hours on days 1, 8, and 15 of each cycle. Administer D5W flush after completion of each tegavivint infusion. Treatment repeats every 28 days for up to 26 cycles or 24 months in the absence of disease progression or unacceptable toxicity. Drug doses should be adjusted based on the weight (height and BSA will also be captured) measured within 7 days prior to the beginning of each cycle. The starting dose will be 5 mg/kg with dose levels for subsequent cohorts increasing to 6.5 mg/kg and 8 mg/kg if excessive toxicity does not occur. If the MTD has been exceeded at the first dose level, then the subsequent cohort of patients will be treated at a dose of 4 mg/kg. Patients undergo an x-ray at baseline, after cycle 1, and then every 3 cycles while on treatment and DEXA scan at baseline and every 6 cycles while on treatment, then at 12 months, 24 months, and annually up to 60 months following end of therapy.
Interventions:
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
147 | ||||
Original Estimated Enrollment ICMJE |
38 | ||||
Estimated Study Completion Date ICMJE | June 30, 2028 | ||||
Estimated Primary Completion Date | June 30, 2028 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 12 Months to 30 Years (Child, Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | |||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04851119 | ||||
Other Study ID Numbers ICMJE | PEPN2011 NCI-2021-02852 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PEPN2011 ( Other Identifier: Pediatric Early Phase Clinical Trial Network ) PEPN2011 ( Other Identifier: CTEP ) UM1CA228823 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | Children's Oncology Group | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Children's Oncology Group | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
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PRS Account | Children's Oncology Group | ||||
Verification Date | April 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |