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
3 other identifiers
interventional
147
1 country
21
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2021
Longer than P75 for phase_1
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2021
CompletedFirst Posted
Study publicly available on registry
April 20, 2021
CompletedStudy Start
First participant enrolled
November 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2028
May 5, 2026
January 1, 2026
6.6 years
April 12, 2021
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Frequency of dose limiting toxicities of tegavivint
The number of patients experiencing a cycle 1 dose limiting toxicity at least possibly attributable to tegavivint by study part and dose level.
Up to 28 days
Frequency of adverse events attributable to tegavivint
The number of patients experiencing adverse events that are at least possibly attributable to tegavivint by study part and dose level.
Up to 60 months
Area under the drug concentration curve of tegavivint
The median (minimum \[min\], maximum \[max\]) of the area under the drug concentration curve for tegavivint by study part and dose level.
Up to 2 days
Secondary Outcomes (1)
Antitumor effects of tegavivint in patients with solid tumors
Up to 336 days
Study Arms (1)
Treatment (tegavivint)
EXPERIMENTALTegavivint 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
Undergo blood sample collection
Undergo DEXA scan
Undergo x-ray imaging
Eligibility Criteria
You may qualify if:
- PART A: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
- PART B: Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
- Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
- PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
- PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
- PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
- PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
- 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 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, e.g., blood count criteria, the patient is considered to have recovered adequately.
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
- Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Non-Hodgkin lymphoma patients
- A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \[6MP\], and/or methotrexate)
- \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
- NOTE: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy
- +27 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study 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 (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
- 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 are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
- Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
- Patients who have received denosumab within 180 days prior to study enrollment will be excluded
- Patients with primary brain tumors are ineligible
- Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
- Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
- Patients with a disorder associated with abnormal bone metabolism will be excluded
- Patients with grade \>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
- Patients with vitamin D \< 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
- Patients with pre-existing grade 3 osteoporosis are excluded
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (21)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sarah B Whittle
Pediatric Early Phase Clinical Trial Network
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2021
First Posted
April 20, 2021
Study Start
November 8, 2021
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
June 30, 2028
Last Updated
May 5, 2026
Record last verified: 2026-01