Neoplasms

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Behaviors and Mental Disorders

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Sarcoma

Lymphoma

Adenocarcinoma

Recurrence

Melanoma

Osteosarcoma

Wilms Tumor

Neuroblastoma

Sarcoma, Ewing

Fibromatosis, Aggressive

Hepatoblastoma

Lymphoma, Non-Hodgkin

Colorectal Neoplasms

Endometrial Neoplasms

Aggression

Fibroma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Disease Attributes

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neoplasms, Connective and Soft Tissue

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endocrine Gland Neoplasms

Endocrine System Diseases

Kidney Neoplasms

Urologic Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Neoplasms, Fibrous Tissue

Pancreatic Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Soft Tissue Sarcoma

Lymphosarcoma

Wilms' Tumor

Ewing Sarcoma

Desmoid Tumor

Neuroepithelioma

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.

Biospecimen Collection

Dual X-ray Absorptiometry

Tegavivint

X-Ray Imaging

Site Public Contact

Girish Dhall

Fariba Navid

Josephine H. Haduong

Kieuhoa T. Vo

Margaret E. Macy

AeRang Kim

William T. Cash

Elizabeth A. Sokol

Melissa K. Bear

Steven G. DuBois

Rajen Mody

Emily G. Greengard

Shalini Shenoy

Luca Szalontay

Joseph G. Pressey

Theodore W. Laetsch

Andrew Bukowinski

Jessica Gartrell

Jennifer H. Foster

Katherine G. Tarlock

Sarah B Whittle

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.

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.

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

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

The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity at least possibly attributable to tegavivint by study part and dose level.

The frequency (%) of patients experiencing adverse events that are at least possibly attributable to tegavivint by study part and dose level.

The median (minimum \[min\], maximum \[max\]) of the area under the drug concentration curve for tegavivint by study part and dose level.

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.

National Cancer Institute (NCI)

Children's Oncology Group

Spots Global Cancer Trial Database for refractory desmoid fibromatosis