PEPN2011: Tegavivint Treatment for Solid Tumors, Lymphomas, and Desmoid Tumors

This is a phase 1 and phase 2 study that investigates the use of the drug tegavivint in children, adolescents, and young adults with recurrent or refractory solid tumors, including lymphomas and desmoid tumors.

Tegavivint is a novel small-molecule inhibitor of Wnt-beta-catenin signaling. Aberrant Wnt signaling has been identified as a key mechanism of cancer biology, resulting in uncontrolled transcription of Wnt target genes, several of which are oncogenes. Tegavivint prevents transcription of Wnt target genes.

Tegavivint inhibits nuclear beta-catenin and oncogenic gene transcription without affecting other important, non-oncogenic cellular functions. Pre-clinical in vivo studies demonstrate anti-tumor activity in a variety of pediatric solid tumors, including osteosarcoma, Ewing sarcoma, and lymphoma. A phase 1/2 study of tegavivint in adults with progressive desmoid tumors has shown promising results and has been well-tolerated with no dose-limiting toxicities.

Primary objective

• Phase 1 (Part A) is complete. We determined the maximum tolerated dose and/or recommended phase 2 (Part B) dosing of tegavivint.
• Phase 2 (Part B) expansion cohort will preliminarily define the antitumor activity of tegavivint. This part is now open to accrual for specific diagnoses including Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors, Wilms tumor, and tumors with Wnt pathway aberrations.

Eligibility criteria

• 12 months to 30 years
• Diagnosis of recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors verified by histology at original diagnosis or relapse

For phase 2 expansion cohort:

• Recurrent or refractory Ewing sarcoma
• Desmoid tumors
• Osteosarcoma
• Hepatocellular carcinoma
• Hepatoblastoma
• Wilms tumor
• Tumors with Wnt pathway aberrations: CTNNB1 mutations, loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5
• If no prior sequencing is available, immunohistochemistry is required, showing strong nuclear beta-catenin staining for colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, or solid pseudopapillary tumor of the pancreas
• Measurable disease: for desmoid tumors, it must be unresectable or sufficiently morbid or potentially life-threatening for a favorable risk/benefit for trial participation
• DEXA scan z-score at baseline greater than -2 from the whole body less the head or lumbar spine sites  

Exclusion criteria

• Pregnant or breastfeeding
• Known CNS metastatic disease, except for craniopharyngeal tumors
• Known metabolic bone disease
• Disorder associated with abnormal bone metabolism
• Grade >/= 2 hypocalcemia not corrected with oral calcium supplementation
• Vitamin D </= 20 mg/mL will require supplementation or will otherwise be excluded
• Pre-existing grade 3 osteoporosis

Study sites

St. Jude and other locations in the U.S.

About this study

In this clinical trial, we will study how well the medicine tegavivint treats certain solid tumors that have come back after treatment (relapsed) or did not respond to treatment (refractory).

Tegavivint has been studied in adults with cancer. We will study how well it works in children, teens, and young adults. This drug helps block a certain cell pathway that is important in the growth of cancer cells. We will study this medicine in children and young adults who have:

• Ewing sarcoma
• Desmoid tumors
• Osteosarcoma
• Liver tumors
• Wilms tumor
• Tumors with a genetic change (mutation) in a gene called Wnt

There are 2 phases, or parts, to this clinical trial:

• Phase 1 (or Part A) is complete. It helped us decide the best dose of tegavivint to use, and we studied the side effects.
• Phase 2 (or Part B) is now open to accept eligible patients. We will use the dose we decided on in phase 1 to study how well tegavivint works.

Purpose of this clinical trial

The main purpose of this study is to find out how well the medicine tegavivint works to help children, teens, and young adults with certain recurrent or refractory solid tumors.

Eligibility overview

To take part in this study, you must be:

• 12 months to 30 years old
• Have a recurrent or refractory solid tumor, including non-Hodgkin lymphoma or desmoid tumor
• For phase 2: you must have recurrent or refractory Ewing sarcoma, desmoid tumor, osteosarcoma, liver tumor (hepatocellular carcinoma or hepatoblastoma), Wilms tumor, or a tumor that has certain changes in the Wnt gene.