Tegavivint for Recurrent or Refractory Cancer

Recruiting in Palo Alto (17 mi)

+22 other locations

Overseen by Sarah B Whittle

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inducers/inhibitors, Bisphosphonates

Disqualifiers: Pregnancy, Brain tumors, CNS metastasis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You cannot be on other anti-cancer agents, investigational drugs, or medications that strongly affect the enzyme CYP3A4. If you are on corticosteroids, you must be on a stable or decreasing dose for at least 7 days before joining the trial.

What makes the drug Tegavivint unique for treating recurrent or refractory cancer?

Tegavivint is unique because it targets the TBL1 (Transducin Beta-Like Protein 1) pathway, which is different from many other cancer treatments that often target more common pathways like ALK or EGFR. This novel mechanism may offer a new option for patients whose cancers do not respond to existing therapies. ^{1 2 3 4 5}

Research Team

Sarah B Whittle

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Eligibility Criteria

This trial is for young people aged up to 21 or 30 years with recurrent or refractory solid tumors, including lymphomas and desmoid tumors. They must have measurable disease, be recovered from previous cancer treatments, meet specific blood count criteria, and not have severe bone diseases or uncontrolled infections. Pregnant individuals can't participate and those of reproductive potential must use effective birth control.

Inclusion Criteria

I have a tumor that cannot be removed by surgery or is dangerous, and it can be measured.

I have a tumor that cannot be removed by surgery or is serious enough to consider treatment.

I have had a stem cell infusion, with or without full-body radiation.

Exclusion Criteria

Patients who are currently receiving another investigational drug are not eligible

I do not have a known metabolic bone disease.

Patients who have received a prior solid organ transplantation are not eligible

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tegavivint IV over 4 hours on days 1, 8, and 15 of each 28-day cycle, for up to 26 cycles or 24 months

24 months

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Every 3 months

Long-term Follow-up

Participants are monitored annually for long-term safety and effectiveness

60 months

Annually

Treatment Details

Interventions

• Tegavivint (Beta-catenin/TBL1 Inhibitor)

Trial Overview The trial is testing Tegavivint's highest safe dose and its effects on patients with stubborn solid tumors that resist treatment. Tegavivint aims to block tumor growth by disrupting signals within cells that encourage cell proliferation.

Participant Groups

Group I: Treatment (tegavivint) Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Dr. Doug Hawkins

Children's Oncology Group

Chief Executive Officer since 2020

MD from University of Washington School of Medicine

Dr. Leo Mascarenhas

Children's Oncology Group

Chief Medical Officer since 2024

MD, MS from Cedars-Sinai Guerin Children’s

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

For patients with relapsed or progressive non-small cell lung cancer (NSCLC), treatment options are limited after conventional chemotherapy, with only erlotinib and crizotinib approved as third-line therapies in the U.S.

The review emphasizes the importance of identifying molecular characteristics of tumors to improve the effectiveness of targeted therapies, suggesting that agents affecting multiple pathways may offer significant clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). Langer, CJ., Mok, T., Postmus, PE.[2022]

In a study of 77 women with HER2-positive, trastuzumab-resistant advanced breast cancer, vinorelbine-based therapy showed an overall response rate of 28% and a clinical benefit rate of 50%, indicating its potential effectiveness as a salvage treatment.

The median time to progression was 7.1 months and the median overall survival was 21 months after starting vinorelbine-based therapy, suggesting that it can provide meaningful clinical benefits in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study. Montemurro, F., Redana, S., Nolè, F., et al.[2021]

PF-06463922 is a next-generation ALK inhibitor that shows significantly higher potency than crizotinib against various ALK mutations, including those that confer resistance, such as F1174L and F1245C.

In preclinical studies, PF-06463922 induced complete tumor regression in both crizotinib-resistant and sensitive neuroblastoma models, suggesting it could be a promising treatment option for children with ALK-mutated neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Infarinato, NR., Park, JH., Krytska, K., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of Relapsed and Refractory ALK-Positive Anaplastic Large Cell Lymphoma With ALK-Specific Tyrosine Kinase Inhibitor in Children: A Case Series. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

Ceritinib Treatment for Carcinomatous Meningitis with a Secondary Mutation at I1171T in Anaplastic Lymphoma Kinase. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. [2022]