Chemo + Radiation Therapy + Dostarlimab for Endometrial Cancer

Overseen By Pamela T. Soliman

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, Immunodeficiency, Hepatitis, others

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

Compensation: Varies

Number of Visits: 6

21 Participants Needed

Trial Summary

Do I need to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain medications are prohibited, and you should consult with the study team to see if your current medications are allowed.

What data supports the effectiveness of the drug combination of chemo, radiation therapy, and dostarlimab for endometrial cancer?

Research shows that the combination of paclitaxel and carboplatin is active against advanced or recurrent endometrial cancer, with some patients experiencing significant tumor reduction. Additionally, using cisplatin with radiation therapy followed by carboplatin and paclitaxel has been reported as a treatment approach for stage III endometrial cancer. ^{1 2 3 4 5}

Is the combination of carboplatin, paclitaxel, and dostarlimab safe for treating endometrial cancer?

Studies show that the combination of carboplatin and paclitaxel is generally active against endometrial cancer, but it can cause significant side effects like grade 3 or 4 hematologic toxicity (serious blood-related side effects) and neuropathy (nerve damage). There was one possible treatment-related death reported, indicating that while the treatment can be effective, it also carries risks. ^{1 2 5 6 7}

What makes the combination of chemo, radiation therapy, and dostarlimab unique for treating endometrial cancer?

This treatment is unique because it combines chemotherapy and radiation with dostarlimab, an immunotherapy drug that helps the immune system fight cancer, potentially offering a new approach for endometrial cancer that may not respond well to standard treatments. ^{1 2 4 5 8}

What is the purpose of this trial?

To learn if chemotherapy given in combination with radiation therapy, followed by maintenance therapy, can help to control endometrial cancer. The safety and effects of this study treatment will also be studied

Research Team

Pamela T. Soliman

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with stage IIIC, node-positive endometrial cancer who've had surgery. They should have good blood counts, kidney and liver function, and no major illnesses that could affect the study. People can't join if they've had certain vaccines recently, uncontrolled diseases, prior treatment with specific antibodies like Dostarlimab or have autoimmune diseases.

Inclusion Criteria

My blood clotting levels are within the normal range or properly managed if I'm on blood thinners.

My liver is functioning well according to recent tests.

Has read and understands the informed consent form (ICF) and has given written informed consent prior to any study procedures

Exclusion Criteria

I am a woman who can still have children and have not been sterilized.

Have received any of the prohibited medications listed in Section 7.2

I have brain complications from cancer, like swelling or bleeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive chemoradiation with concurrent immunotherapy

6 cycles

Chemotherapy + Immunotherapy

Participants receive chemotherapy plus concurrent immunotherapy

6 cycles

Maintenance Therapy

Participants receive maintenance immunotherapy

14 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up every 6 months

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Dostarlimab
• Paclitaxel

Trial Overview The trial tests a combination of chemotherapy drugs (Paclitaxel and Carboplatin) with radiation therapy followed by maintenance therapy using Dostarlimab to see if it controls endometrial cancer better and what side effects it might cause.

Participant Groups

Group I: Immunotherapy after Radiation and Chemo Experimental Treatment 4 Interventions

Participants will receive an active treatment for 6 cycles. Participants will be on maintenance for 14 cycles, as long as the disease does not get worse. Follow-up will then occur every 6 months for 5 years (from your enrollment date).

Group II: Adjuvant Therapy During Radiation Experimental Treatment 4 Interventions

Participants will receive an active treatment for 6 cycles. Participants will be on maintenance for 14 cycles, as long as the disease does not get worse. Follow-up will then occur every 6 months for 5 years (from your enrollment date).

Group III: Adjuvant Therapy After Radiation Experimental Treatment 4 Interventions

Participants will receive an active treatment for 6 cycles. Participants will be on maintenance for 14 cycles, as long as the disease does not get worse. Follow-up will then occur every 6 months for 5 years (from your enrollment date).

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a study of 39 patients with metastatic or recurrent endometrial carcinoma, the combination of paclitaxel, topotecan, and carboplatin resulted in a 60% objective clinical response rate, indicating significant efficacy in treating this cancer.

The treatment was associated with manageable toxicity, with only 13% of patients experiencing severe thrombocytopenia and 10% experiencing severe neutropenia, suggesting that the regimen is relatively safe for outpatient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, topotecan, and carboplatin in metastatic endometrial cancinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. Papadimitriou, CA., Fountzilas, G., Bafaloukos, D., et al.[2015]

The combination of paclitaxel and carboplatin showed promising activity in treating endometrial cancer resistant to standard therapies, with 63% of evaluable patients experiencing a significant reduction in tumor size.

While the treatment had acceptable toxicity levels, with some patients experiencing grade 3 or 4 hematologic issues, further follow-up is needed to assess long-term survival outcomes and the overall effectiveness of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. Price, FV., Edwards, RP., Kelley, JL., et al.[2016]

The combination of dose-dense paclitaxel and carboplatin was found to be a feasible treatment option for advanced or recurrent endometrial cancer, with a response rate of 71.3% among 46 eligible participants.

Out of the 48 enrolled women, 63% completed six or more cycles of chemotherapy, indicating that the treatment regimen is manageable and tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial. Hori, K., Nishio, S., Ushijima, K., et al.[2021]

In a study of 40 patients with stage III endometrial cancer, the combination of concurrent external beam radiation therapy and cisplatin followed by carboplatin/paclitaxel resulted in a 5-year freedom from relapse rate of 79% and an overall survival rate of 85%.

The treatment was well-tolerated, with 78% of patients completing the planned therapy and only 10 patients experiencing acute grade 3 toxicity, while no late toxicity was reported at grade 3 or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative external beam radiation therapy and concurrent cisplatin followed by carboplatin/paclitaxel for stage III (FIGO 2009) endometrial cancer. Milgrom, SA., Kollmeier, MA., Abu-Rustum, NR., et al.[2020]

In a study of 18 patients with advanced or recurrent endometrial cancer, the combination of carboplatin and paclitaxel showed a high overall response rate of 63%, with 35% achieving a complete response.

The treatment demonstrated minimal toxicity, as no patients experienced severe side effects like neutropenia or significant vomiting, and the median survival time was 27 months, indicating it is a promising option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Akram, T., Maseelall, P., Fanning, J.[2015]

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 study of 18 patients with recurrent or advanced endometrial adenocarcinoma, a combination chemotherapy of cisplatin, doxorubicin, and cyclophosphamide resulted in a 56% objective response rate, with 28% achieving complete response and 28% achieving partial response.

The treatment was effective even in patients who had previously undergone irradiation and failed hormonal therapy, although it did lead to myelosuppression in seven patients and neurotoxicity in two.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium. Hancock, KC., Freedman, RS., Edwards, CL., et al.[2013]

References

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

Paclitaxel, topotecan, and carboplatin in metastatic endometrial cancinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. [2015]

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

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. [2016]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial. [2021]

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

Postoperative external beam radiation therapy and concurrent cisplatin followed by carboplatin/paclitaxel for stage III (FIGO 2009) endometrial cancer. [2020]

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

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. [2015]

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

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

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

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

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

Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium. [2013]