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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining chemotherapy and radiation therapy, followed by a maintenance phase, can effectively manage endometrial cancer. The study will also assess the safety of this treatment and its effects on patients. Participants will receive different treatment plans, including chemotherapy during or after radiation, and some may receive additional immunotherapy with Dostarlimab, which helps the immune system fight cancer. Those with stage IIIC endometrial cancer who have undergone surgery within the last 8 weeks may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

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

A previous study showed that carboplatin and paclitaxel are well tolerated for treating advanced endometrial cancer. Most side effects were mild, though some patients experienced more severe reactions like anemia. Paclitaxel, another drug in the same group, has also been generally well-tolerated, with few reports of allergic reactions.

Cisplatin, a strong chemotherapy drug, can have significant side effects. Many patients report hearing loss and other serious concerns. While effective for many cancers, it comes with these risks.

Dostarlimab, a newer treatment, has been tested in patients with advanced endometrial cancer. It improved survival when combined with carboplatin and paclitaxel. The safety profile of dostarlimab was evaluated in several patients, showing that while generally safe, some patients may experience side effects of varying severity.

These treatments have been studied both separately and in combination. While generally safe, the level of side effects varies. Participants should discuss these findings with their doctors to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they combine traditional chemotherapy and radiation with dostarlimab, an innovative immunotherapy. While standard treatments like carboplatin, cisplatin, and paclitaxel focus on killing cancer cells directly, dostarlimab works differently by activating the immune system to recognize and destroy cancer cells. This combination approach aims to enhance the effectiveness of treatment by not only attacking the cancer itself but also boosting the body's natural defenses. Additionally, the trial explores different timing strategies for administering these therapies, which could lead to more personalized and effective treatment plans.

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

Research has shown that using carboplatin and paclitaxel together can extend the lives of patients with advanced or recurrent endometrial cancer. In some studies, tumors shrank in 50% of women treated with this combination. In this trial, participants in different arms will receive various combinations of these treatments. Research suggests that cisplatin works well, but it might not prevent cancer recurrence when used with radiation in certain cases. Dostarlimab, combined with carboplatin and paclitaxel, has significantly slowed the cancer's growth and spread. Overall, combining these treatments appears promising for improving outcomes in fighting endometrial cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Pamela T. Soliman

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7676887/

Carboplatin and Paclitaxel for Advanced Endometrial Cancer This was the first trial to show a survival advantage for combination chemotherapy in patients with measurable advanced or recurrent endometrial cancer. For ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352578919300414

Retreatment with carboplatin and paclitaxel for recurrent ... Re-exposure to paclitaxel and carboplatin chemotherapy resulted in tumor shrinkage in 50% of women with endometrial cancer. 15% of patients with recurrent ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00721-X/fulltext

Overall survival in patients with endometrial cancer treated ... An improvement of 13.9 months in median PFS2 was observed in patients receiving dostarlimab plus carboplatin–paclitaxel (median PFS2 of 32.3 ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11654-z

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel ... Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.16591

Comparison of the efficacy between paclitaxel/carboplatin ... Conclusions: Paclitaxel/carboplatin may have comparable efficacy and lower toxicity with lesser administration than doxorubicin/cisplatin for ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5599

Safety and tolerability of durvalumab + carboplatin ... The most common AEs were mostly low grade, with grade 3/4 in few pts (anemia [14%, 16%, 24% in the CP, CP+D, CP+D+O arms, respectively], ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S095980490200504X

Phase II study of carboplatin in patients with advanced or ... Our study indicates that carboplatin is safe and active in advanced endometrial cancer. ... risk stage I endometrial cancer: A national cancer data base analysis.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00584909

A Phase II Study of Paclitaxel and Carboplatin in Patients ... The safety of this combination is well established in a number of phase III trials and currently is used in the primary setting for patients with ovarian cancer ...