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

Who is this study for? Patients with Cancer
Status: Recruiting
Location: See all (21) locations...
Intervention Type: Procedure, Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 30
Healthy Volunteers: f
View:

• 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

⁃ Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent

⁃ Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1

⁃ Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid

⁃ Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur

⁃ Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)

⁃ Stem cell Infusions (with or without total-body irradiation \[TBI\]):

• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)

∙ Autologous stem cell infusion including boost infusion: \>= 42 days.

⁃ Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).

⁃ External beam radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation

⁃ Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy

⁃ Patients must not have received prior exposure to tegavivint

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \>= 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)

• Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):

‣ Age; maximum serum creatinine

⁃ Age 1 to \< 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)

⁃ Age \>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)

• PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS: Albumin \>= 2 g/dL (within 7 days prior to enrollment)

Locations
United States
Alabama
Children's Hospital of Alabama
RECRUITING
Birmingham
California
Children's Hospital Los Angeles
RECRUITING
Los Angeles
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
ACTIVE_NOT_RECRUITING
Palo Alto
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington D.c.
Georgia
Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITING
Atlanta
Illinois
Lurie Children's Hospital-Chicago
RECRUITING
Chicago
Indiana
Riley Hospital for Children
RECRUITING
Indianapolis
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Minnesota
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Missouri
Washington University School of Medicine
RECRUITING
St Louis
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
Ohio
Cincinnati Children's Hospital Medical Center
RECRUITING
Cincinnati
Pennsylvania
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Tennessee
Saint Jude Children's Research Hospital
RECRUITING
Memphis
Texas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Time Frame
Start Date: 2021-11-08
Estimated Completion Date: 2028-06-30
Participants
Target number of participants: 147
Treatments
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.
Sponsors
Leads: Children's Oncology Group
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov