Zanzalintinib + Paclitaxel for Uterine Cancer

Recruiting at 3 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

Trial Summary

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.

What data supports the effectiveness of the drug combination Zanzalintinib and Paclitaxel for uterine cancer?

Research shows that Paclitaxel, when used with other drugs like carboplatin, has been effective in treating advanced or recurrent endometrial cancer, which is a type of uterine cancer. This suggests that Paclitaxel could be beneficial in combination with Zanzalintinib for similar conditions. ^{1 2 3 4 5}

What safety information is available for Paclitaxel in cancer treatment?

Paclitaxel, used in various cancer treatments, can cause side effects like myelosuppression (reduced bone marrow activity), mucositis (inflammation of the digestive tract lining), neurotoxicity (nerve damage), hypersensitivity reactions, heart rhythm changes, joint and muscle pain, hair loss, and mild nausea. Dermatological issues affecting skin, hair, and nails are also common with taxane chemotherapy, which includes paclitaxel. ^{6 7 8 9 10}

How is the drug combination of Zanzalintinib and Paclitaxel unique for treating uterine cancer?

The combination of Zanzalintinib and Paclitaxel for uterine cancer is unique because it introduces Zanzalintinib, a novel agent, alongside Paclitaxel, which is already known for its activity in various cancers. This combination may offer a new approach by potentially enhancing the effectiveness of Paclitaxel, although specific details about Zanzalintinib's role in uterine cancer are not yet well-documented. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this study is to determine the recommended Phase 2 dose of zanzalintinib when given in combination with paclitaxel in patients with recurrent high-grade uterine cancer. Other objectives include overall safety and tolerability as well as rates of response.

Research Team

David G Mutch, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

I am taking specific blood thinners.

Other conditions compromising patient safety or ability to complete the study

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

References

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

Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. [2022]

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

Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. [2015]

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

Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. [2015]

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

Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study. [2022]

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

Evaluation of paclitaxel in previously treated leiomyosarcoma of the uterus: a gynecologic oncology group study. [2019]

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

Chronic administration of single-agent paclitaxel in gynecologic malignancies. [2015]

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

Paclitaxel (taxol). [2019]

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

Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium: Japanese Multicenter Study Group. [2015]

9. United States 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. [2018]

10. France pubmed.ncbi.nlm.nih.gov

Dermatological adverse events with taxane chemotherapy. [2022]

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

Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. [2015]

12. Japan pubmed.ncbi.nlm.nih.gov

A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer. [2021]

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

The platinum compounds and paclitaxel in the management of carcinomas of the endometrium and uterine cervix. [2015]

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

Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. [2021]

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

Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. [2017]