Recruitment

Recruitment Status
Not yet recruiting

Inclusion Criteria

Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
...
Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
Age 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age
NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
Age 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Age 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
PART B: Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
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 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
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.).
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
Age 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
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
PART A: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
Age >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
Age 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
Autologous stem cell infusion including boost infusion: >= 42 days.
A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine [6MP], and/or methotrexate)
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)
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 WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
Patients must not have received prior exposure to tegavivint
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
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
PATIENTS WITH SOLID TUMORS: Albumin >= 2 g/dL
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
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
Age; maximum serum creatinine
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
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)
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
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

Exclusion Criteria

Patients who are currently receiving another investigational drug are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
...
Patients who are currently receiving another investigational drug are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients with a disorder associated with abnormal bone metabolism will be excluded
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 have received bisphosphonates within 4 weeks prior to study enrollment 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 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 with grade >= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
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 who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Patients with pre-existing grade 3 osteoporosis are excluded
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 have received denosumab within 180 days prior to study enrollment will be excluded
Patients who have an uncontrolled infection are not eligible
Patients with primary brain tumors are ineligible
Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
Patients with known central nervous system (CNS) metastasis will be excluded

Summary

Conditions
  • Melanoma
  • Colorectal Carcinoma
  • Refractory Osteosarcoma
  • Solid Pseudopapillary Neoplasm of the Pancreas
  • Refractory Non Hodgkin Lymphoma
  • Recurrent Non-Hodgkin Lymphoma
  • Refractory Malignant Solid Neoplasm
  • Endometrial Carcinoma
  • Recurrent Osteosarcoma
  • Refractory Ewing Sarcoma
  • Neuroblastoma
  • Ovarian Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Recurrent Desmoid Fibromatosis
  • Recurrent Ewing Sarcoma
  • Recurrent Hepatoblastoma
  • Refractory Hepatocellular Carcinoma
  • Refractory Desmoid Fibromatosis
  • Wilm's Tumor
  • Refractory Hepatoblastoma
  • Recurrent Hepatocellular Carcinoma
  • Recurrent Malignant Solid Neoplasm
Type
Interventional
Phase
Phase 1Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 1230 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of tegavivint administered as an 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, in...

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of tegavivint administered as an 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. OUTLINE: Patients receive tegavivint intravenously (IV) over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. 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.

Inclusion Criteria

Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
...
Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
Age 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age
NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
Age 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Age 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
PART B: Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
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 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
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.).
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
Age 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
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
PART A: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
Age >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
Age 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
Autologous stem cell infusion including boost infusion: >= 42 days.
A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine [6MP], and/or methotrexate)
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)
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 WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
Patients must not have received prior exposure to tegavivint
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
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
PATIENTS WITH SOLID TUMORS: Albumin >= 2 g/dL
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
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
Age; maximum serum creatinine
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
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)
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
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

Exclusion Criteria

Patients who are currently receiving another investigational drug are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
...
Patients who are currently receiving another investigational drug are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients with a disorder associated with abnormal bone metabolism will be excluded
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 have received bisphosphonates within 4 weeks prior to study enrollment 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 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 with grade >= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
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 who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Patients with pre-existing grade 3 osteoporosis are excluded
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 have received denosumab within 180 days prior to study enrollment will be excluded
Patients who have an uncontrolled infection are not eligible
Patients with primary brain tumors are ineligible
Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
Patients with known central nervous system (CNS) metastasis will be excluded

Tracking Information

NCT #
NCT04851119
Collaborators
Not Provided
Investigators
  • Principal Investigator: Jade Wulff Pediatric Early Phase Clinical Trial Network
  • Jade Wulff Pediatric Early Phase Clinical Trial Network
  • Sarah B Whittle Pediatric Early Phase Clinical Trial Network