Zanzalintinib + Paclitaxel for Uterine Cancer

Recruiting at 4 trial locations

Overseen By David G Mutch, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Other malignancy, Brain metastases, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 9

Duration: 27 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combining zanzalintinib (a potential new drug) and paclitaxel for women with certain types of recurrent, high-grade uterine cancer. Researchers aim to determine the best dose of zanzalintinib to use with paclitaxel and assess the safety and effectiveness of this combination. This study may suit those who have not responded to platinum-based treatments for their uterine cancer and cannot undergo surgery or radiation. 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 combination.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have taken certain treatments like small molecule kinase inhibitors or other investigational agents within a few weeks before starting the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that using zanzalintinib with paclitaxel can help treat certain cancers. This combination has allowed patients to live without their cancer worsening for about 15 months on average and to live for about 25 months on average overall.

Regarding safety, the study remains in its early stages. Researchers are closely monitoring the safety of the zanzalintinib and paclitaxel combination. Early trials focus on understanding treatment tolerance and identifying any side effects. Researchers prioritize ensuring the treatment's safety for participants.

While more information is needed to fully understand its safety, paclitaxel is already a well-known cancer treatment. Its effects are widely studied and documented, providing some context for safety. However, zanzalintinib is still under evaluation, so participants will be carefully monitored to ensure their safety throughout the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Zanzalintinib combined with Paclitaxel for uterine cancer because it offers a new approach to treatment. While most current treatments for uterine cancer focus on chemotherapy alone, Zanzalintinib adds a novel compound that may enhance the effectiveness of the standard chemotherapy, Paclitaxel. This combination could potentially improve patient outcomes by targeting cancer cells more effectively, possibly leading to quicker and more sustained responses. By integrating Zanzalintinib, researchers hope to boost the therapeutic impact beyond what traditional chemotherapy offers, thereby paving the way for better management of uterine cancer.

What evidence suggests that this trial's treatments could be effective for uterine cancer?

Research has shown that combining zanzalintinib and paclitaxel may help treat aggressive uterine cancer. In this trial, participants will receive different dose levels of the combination treatment. Previous studies indicated that patients who received this combination treatment experienced an average of 15 months before their cancer began growing again. On average, these patients lived for 25 months after starting the treatment. These findings suggest that this treatment could effectively manage recurring uterine cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

David G Mutch, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for women over 18 with recurrent high-grade uterine cancer who've had prior platinum-based therapy and can't be treated locally. They should have recovered from previous treatments, have measurable disease, good performance status, normal organ function, agree to contraception if of child-bearing potential, and not be pregnant. Up to two prior anti-cancer therapies are allowed.

Inclusion Criteria

I have recovered from side effects of previous treatments.

Measurable disease by RECIST 1.1

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have been treated with zanzalintinib before.

Other conditions compromising patient safety or ability to complete the study

Clinically significant disorders that would preclude safe study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib in combination with paclitaxel on a 21-day cycle. After 3 cycles, response is assessed. Treatment may continue for up to 9 cycles based on response.

27 weeks

9 visits (in-person)

Maintenance

Participants with stable disease or partial response after 9 cycles continue on maintenance zanzalintinib until progression.

Until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Zanzalintinib

Trial Overview

The study aims to find the best dose of zanzalintinib combined with paclitaxel for treating high-grade uterine cancer. It will assess safety, tolerability, and how well patients respond to this combination treatment.

How Is the Trial Designed?

Group I: Dose Level 3: Zanzalintinib + Paclitaxel Experimental Treatment 2 Interventions

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Group II: Dose Level 2 (Starting Dose): Zanzalintinib + Paclitaxel Experimental Treatment 2 Interventions

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Group III: Dose Level 1 (Reduction): Zanzalintinib + Paclitaxel Experimental Treatment 2 Interventions

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

In a phase II study involving 53 patients with persistent or recurrent carcinosarcoma of the uterus, paclitaxel demonstrated moderate clinical activity, with an overall response rate of 18.2%, including both complete and partial responses.

The most common side effect observed was neutropenia, indicating that while paclitaxel can be effective, it also carries risks that need to be monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study. Curtin, JP., Blessing, JA., Soper, JT., et al.[2022]

In a study of 47 patients with advanced or recurrent endometrial carcinoma, the combination of carboplatin and paclitaxel resulted in a high overall response rate of 62%, with 21% achieving complete responses and 41% partial responses.

The treatment demonstrated a median progression-free survival of 15 months and a median overall survival of 25 months, indicating its effectiveness, while the toxicity was generally mild, though 36% of patients experienced significant neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Pectasides, D., Xiros, N., Papaxoinis, G., et al.[2015]

Taxanes, such as docetaxel and paclitaxel, are widely used anticancer drugs for various cancers, but they are associated with significant dermatological adverse events (AEs) that have not been thoroughly studied in a prospective manner.

Understanding and managing these skin, hair, and nail toxicities is crucial for maintaining the quality of life in cancer patients and preventing necessary dose adjustments in their treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events with taxane chemotherapy. Sibaud, V., Lebœuf, NR., Roche, H., et al.[2022]

In a phase 2 study involving 57 patients with high-risk endometrial cancer, concurrent chemoradiation with weekly paclitaxel was found to be well tolerated, with no life-threatening toxicities reported and most severe side effects being self-limited hematologic issues.

The treatment showed promising efficacy, with a 5-year disease-free survival rate of 63.5% and an overall survival rate of 82.7%, suggesting that this approach could be a viable option for further testing in larger randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 trial of radiation therapy with concurrent paclitaxel chemotherapy after surgery in patients with high-risk endometrial cancer: a Korean Gynecologic Oncologic Group study. Cho, H., Nam, BH., Kim, SM., et al.[2018]

In a study of 37 patients with advanced or recurrent endometrial carcinoma, the combination of paclitaxel and carboplatin resulted in a 61% objective response rate, including one complete response and ten partial responses, indicating its efficacy in treating this cancer.

While the treatment was effective, it was associated with significant hematologic toxicity, with 59% of patients experiencing grade 3 or 4 leukopenia and 86% experiencing neutropenia, highlighting the need for monitoring and potential supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Arimoto, T., Nakagawa, S., Yasugi, T., et al.[2015]

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