Tegavivint for Recurrent or Refractory Cancer

Recruiting at 24 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inducers/inhibitors, Bisphosphonates

Disqualifiers: Pregnancy, Brain tumors, CNS metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 24 months

147 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose and understand the side effects and potential benefits of a new drug, tegavivint, for patients with solid tumors that have returned or don't respond to other treatments. Tegavivint interferes with specific signals that promote tumor cell growth. Patients with recurring or hard-to-treat tumors, such as certain bone and liver cancers, may be suitable candidates for this trial. Participants should have tumors that are not easily removed or are life-threatening. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that tegavivint is likely to be safe for humans?

Research has shown that tegavivint is generally safe for people. Previous studies found mostly mild side effects, such as minor discomfort. Importantly, no serious side effects related to its main purpose were reported, indicating it didn’t cause major harm in the studies conducted so far. In one study, about 62.5% of patients experienced mild side effects, with no severe reactions noted. This suggests that tegavivint could be a safe option for treating certain types of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Tegavivint because it targets a specific protein called beta-catenin, which plays a crucial role in the growth and survival of cancer cells. Unlike many standard treatments, which might not specifically target this pathway, Tegavivint aims to disrupt the Wnt/beta-catenin signaling pathway, offering a new mechanism of action that could be particularly effective for cancers that are resistant to other therapies. Additionally, Tegavivint is administered intravenously, allowing for precise dosing adjustments based on patient weight, potentially reducing toxicity and improving tolerance. This targeted approach could lead to more effective outcomes for patients with recurrent or refractory cancers.

What evidence suggests that tegavivint might be an effective treatment for recurrent or refractory cancer?

Research has shown that tegavivint, the investigational treatment in this trial, may help treat certain cancers. In one study, most patients tolerated it well, experiencing only mild to moderate side effects. Importantly, about 25% of participants saw their tumors shrink. Early results also suggest that tegavivint can slow tumor growth by blocking signals that cancer cells need to grow. In another study with advanced liver cancer, tegavivint showed early signs of being both effective and safe. Overall, these findings are promising for its use in treating recurring or difficult-to-treat cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Sarah B Whittle

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tegavivint

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.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

A lung cancer patient developed an ALK I1171T resistance mutation after treatment with chemotherapy and ALK inhibitors, highlighting the need to investigate resistance mechanisms in clinical practice.

Despite initial ineffectiveness, ceritinib was effective after whole-brain radiotherapy and shunting, suggesting that identifying resistance mutations can help optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceritinib Treatment for Carcinomatous Meningitis with a Secondary Mutation at I1171T in Anaplastic Lymphoma Kinase. Ashinuma, H., Shingyoji, M., Hasegawa, Y., et al.[2019]

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]

In a report involving 3 pediatric patients with relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL), all patients achieved a complete response after treatment with ALK inhibitors.

Both crizotinib and alectinib demonstrated significant effectiveness in treating refractory ALK-positive ALCL in children, including one patient with central nervous system involvement.

NCBI (Pubmed)

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. Shen, D., Song, H., Zhang, J., et al.[2023]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04851119

NCT04851119 | Tegavivint for the Treatment of Recurrent ...

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 ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.11523

Results of a phase I dose escalation and expansion study ...

Tegavivint is well tolerated with mostly Grade 1/2 AEs and no serious toxicity associated with WNT inhibition. The ORR of 25% at the RP2D warrants continued ...

3.

onclive.com

onclive.com/view/tegavivint-demonstrates-preliminary-efficacy-tolerability-in-advanced-hcc

Tegavivint Demonstrates Preliminary Antitumor Activity, ...

Tegavivint demonstrated early efficacy and safety in advanced HCC, with low-grade TRAEs in 62.5% of patients and no grade 4 or 5 TRAEs observed.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9565452/

Preclinical efficacy of the Wnt/β-catenin pathway inhibitor ...

Our preclinical studies provide data on the efficacy of BC2059 in desmoid cell lines, which could help provide insight regarding antitumor ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04874480

Tegavivint for the Treatment of Relapsed or Refractory ...

Tegavivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tegavivint in combination with decitabine may help ...

6.

asco.org

asco.org/abstracts-presentations/ABSTRACT455986

A phase 1/2 study of the TBL1 inhibitor, tegavivint (BC2059 ...

Tegavivint treatment of established β-cateninexon3 activated tumors resulted in reduced tumor growth and burden. Based on these promising preclinical results, ...