Cabozantinib + Dostarlimab for Gynecologic Cancers

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, Cabozantinib and Dostarlimab, for patients with recurrent gynecologic carcinosarcoma. Cabozantinib works by blocking proteins that help tumors grow blood vessels, while Dostarlimab helps the immune system attack cancer cells. The goal is to improve treatment effectiveness by using both drugs together.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had certain cancer treatments or radiation therapy recently. You also cannot take certain blood thinners like warfarin, but some others are allowed if stable.

What data supports the effectiveness of the drug combination Cabozantinib and Dostarlimab for gynecologic cancers?

Dostarlimab has shown effectiveness in treating endometrial cancer, particularly in patients with mismatch repair deficient tumors, with the FDA granting accelerated approval based on tumor response rates. Additionally, a clinical trial reported a 100% remission rate for rectal cancer, suggesting potential benefits in other cancers. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Dostarlimab safe for gynecologic cancers?

Cabozantinib has been studied in various gynecologic cancers, showing it can be tolerated by patients, but specific safety data for the combination with Dostarlimab is not available in the provided research. ^{6 7 8 9 10}

What makes the drug combination of Cabozantinib and Dostarlimab unique for treating gynecologic cancers?

This drug combination is unique because it combines Cabozantinib, which targets cancer cell growth, with Dostarlimab, an immune-checkpoint inhibitor that helps the immune system attack cancer cells. This approach may offer a novel way to treat gynecologic cancers by using both targeted therapy and immunotherapy. ^{2 3 4 5 7}

Research Team

Eligibility Criteria

This trial is for adults with recurrent gynecologic carcinosarcoma who've had at least one chemotherapy treatment. They must have a certain level of hemoglobin, white blood cells, and platelets, no serious illnesses or recent surgeries, and can't be pregnant or breastfeeding. Participants need to agree to use contraception and not have used certain drugs recently.

Inclusion Criteria

Capable of understanding and complying with the protocol requirements and must have signed the informed consent document

My blood tests show my organs and bone marrow are working well.

My cancer is a type called carcinosarcoma.

Exclusion Criteria

I cannot swallow pills.

Medical or psychological impediment to probable compliance with the protocol

I have not had major surgery recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Cabozantinib 40 mg by mouth every day + Dostarlimab 500 mg intravenous every 3 weeks followed by maintenance therapy: Cabozantinib 40 mg by mouth every day + Dostarlimab 1000 mg intravenous every 6 weeks

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cabozantinib (VEGF Inhibitor)
• Dostarlimab (PD-1 Inhibitor)

Trial Overview The study tests Cabozantinib (a drug that inhibits blood vessel growth in tumors) combined with Dostarlimab (an immunotherapy drug) on patients with recurring gynecological cancers. It aims to see if this combination improves the body's immune response against cancer cells.

Participant Groups

Group I: Cabo + Dostarlimab Experimental Treatment 1 Intervention

Cabozantinib 40 mg by mouth every day + Dostarlimab 500 mg intravenous every 3 weeks followed by maintenance therapy: Cabozantinib 40 mg by mouth every day + Dostarlimab 1000 mg intravenous every 6 weeks

Cabozantinib is already approved in Canada, Japan for the following indications:

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

O'Neal Comprehensive Cancer Center at UAB Birmingham, AL

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1677

Patients Recruited

2,458,000+

Findings from Research

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab showed significant antitumor activity in patients with advanced endometrial cancer, achieving an objective response rate (ORR) of 43.5% in those with dMMR/MSI-H disease, compared to 14.1% in those with proficient/stable disease, indicating its potential effectiveness in specific cancer subtypes.

The treatment had a manageable safety profile, with most adverse events being mild to moderate (grade 1-2), and no deaths attributed to the drug, suggesting it is a safe option for patients with advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. Oaknin, A., Gilbert, L., Tinker, AV., et al.[2022]

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

Cabozantinib and temozolomide both significantly reduced the growth and viability of uterine sarcoma cells, with the combination of the two drugs showing even greater effectiveness in promoting cell death and inhibiting tumor growth.

In mouse models, the combined treatment of cabozantinib and temozolomide led to a significant reduction in tumor size, indicating a synergistic effect that supports further clinical trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma. Noh, JJ., Cho, YJ., Ryu, JY., et al.[2022]

In a study involving 111 patients with recurrent ovarian cancer, cabozantinib showed a median progression-free survival (PFS) of 5.3 months, which was similar to the 5.5 months achieved with weekly paclitaxel, indicating comparable initial treatment effectiveness.

However, cabozantinib had worse outcomes in overall survival (OS), event-free survival (EFS), and overall response rate (ORR) compared to paclitaxel, along with increased gastrointestinal side effects, leading to the conclusion that cabozantinib is not recommended for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study. Matulonis, UA., Sill, MW., Makker, V., et al.[2020]

References

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

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

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

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. [2022]

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

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma. [2019]

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

Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma. [2022]

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

Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001). [2023]

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

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study. [2020]

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

Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86). [2021]