Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors

Active:	Yes
Cancer Type:	Brain Tumor Colon/Rectal Cancer Liver Cancer / Hepatoblastoma Melanoma Neuroblastoma Non-Hodgkin Lymphoma Ovarian Cancer Sarcoma Uterine Cancer Wilms Tumor	NCT ID:	NCT04851119
Trial Phases:	Phase I Phase II	Protocol IDs:	PEPN2011 (primary) PEPN2011 NCI-2021-02852
Eligibility:	12 Months - 30 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Pediatric Early Phase Clinical Trial Network
NCI Full Details:	http://clinicaltrials.gov/show/NCT04851119

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.

Objectives

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.

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.