Radiation + Chemotherapy for Endometrial Cancer

Recruiting at 9 trial locations

Overseen By Vicky Makker, MD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: POLE mutations, Mismatch repair deficient, Inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating stage III endometrial cancer. Researchers aim to determine if patients can complete a shorter, one-week course of radiation therapy combined with chemotherapy, instead of the usual five weeks. The study uses specific chemotherapy drugs, carboplatin and paclitaxel, along with advanced radiation techniques. It seeks participants who have had surgery for endometrial cancer, with no remaining visible cancer, and who have not received prior chemotherapy or radiation for this condition. For those meeting these criteria and interested in new treatment methods, this trial might be suitable.

As an Early 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 innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that patients generally tolerate the combination of carboplatin and paclitaxel well. Previous studies have found these drugs to be commonly used and safe for treating ovarian cancer. Doctors are familiar with these medications, and they are considered safe for regular use in certain cancer treatments.

Intensity-modulated radiation therapy (IMRT) has also undergone safety studies. Research suggests that IMRT better targets cancer cells while causing fewer side effects. For example, patients treated with IMRT experienced fewer stomach and intestine issues compared to older radiation types.

Overall, these treatments have been widely used and are known to be safe for many people. Although this study is in an early stage, the treatments involved have a strong history of being well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining carboplatin, intensity-modulated radiation therapy (IMRT), and paclitaxel for endometrial cancer because this approach targets the cancer more precisely while minimizing damage to healthy tissues. Unlike traditional radiation therapies, IMRT allows for more accurate delivery of radiation, potentially leading to fewer side effects. Additionally, the combination of carboplatin and paclitaxel is designed to enhance the overall effectiveness of the treatment by attacking the cancer cells in different ways. This multi-pronged strategy could offer improved outcomes for patients with stage III endometrial cancer compared to standard treatments.

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 people with advanced endometrial cancer. Some studies found that this combination shrinks tumors in about 50% of women with recurring cancer. In this trial, participants will receive this chemotherapy regimen alongside radiation therapy. When combined with radiation, this chemotherapy is safe and effective for high-risk patients. The trial also tests a newer type of radiation therapy, called intensity-modulated radiation therapy (IMRT), which can improve patient outcomes and reduce side effects like stomach problems compared to older methods. Overall, these treatments have shown promise in improving outcomes for endometrial cancer patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Kaled Alektair, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed endometrial carcinoma who've had specific surgeries and have no residual disease. They must not be breastfeeding, have good organ function, and a performance status indicating they can care for themselves. Excluded are those with certain genetic markers or prior treatments, active infections needing antibiotics (except simple UTIs), or conditions that could affect the trial's safety or results.

Inclusion Criteria

Participants must agree not to breastfeed during the study or for 150 days after the last dose of study treatment.

I have another cancer, but it won't affect this trial's treatment.

I am not on antibiotics for an infection, except for a simple UTI.

Exclusion Criteria

Patients with psychiatric or substance use disorders that would interfere with cooperation with the requirements of the trial.

My endometrial cancer lacks certain proteins, confirmed by specific tests.

I am not suitable for pelvic radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive short-course radiation therapy for 1 week

1 week

Chemotherapy

Participants receive carboplatin and paclitaxel chemotherapy

6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Intensity-modulated radiation therapy
• Paclitaxel

Trial Overview The study tests if a shorter radiation therapy course (1 week) combined with chemotherapy drugs carboplatin and paclitaxel is feasible for patients to complete compared to the usual 5-week radiation schedule. It aims to see if participants can stick to this condensed treatment plan without significant issues.

How Is the Trial Designed?

Group I: Participants with Endometrial Cancer Experimental Treatment 3 Interventions

Participants have stage III endometrial cancer

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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]

A study of 31 patients with high-risk or advanced endometrial cancer showed that concurrent chemotherapy with paclitaxel and carboplatin, along with radiotherapy, resulted in excellent local-regional control, with 5-year progression-free survival rates of 79%.

While the treatment was feasible and well tolerated, with manageable side effects, distant metastases were still observed in advanced-stage patients, indicating a need for further research to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant paclitaxel plus carboplatin and radiotherapy for high-risk or advanced endometrial cancer. Wen, Q., Shao, Z., Yang, Z.[2018]

A treatment regimen of docetaxel and carboplatin followed by targeted radiation was found to be feasible and effective for patients with advanced stage endometrial cancer, with a median overall survival of 74.5 months and 1-year overall survival rate of 84.5%.

The study involved 45 patients, with 76% completing the therapy; while there were serious toxicities, the treatment demonstrated acceptable safety and efficacy, making it a viable option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II evaluation of docetaxel and carboplatin followed by tumor volume directed pelvic plus or minus paraaortic irradiation for stage III endometrial cancer. Scribner, DR., Puls, LE., Gold, MA.[2018]

The study determined that the maximum tolerated dose (MTD) of paclitaxel in combination with carboplatin and pelvic IMRT for early-stage cervical cancer patients is 35 mg/m², with an area under the curve (AUC) of 2.0.

Acute dose-limiting toxicities (DLTs) were observed at higher doses, including grade 2 hypersensitivity and grade 3 leukopenia and neutropenia, indicating that careful monitoring is necessary when administering this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of concurrent weekly carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes. Mabuchi, S., Takahashi, R., Isohashi, F., et al.[2020]

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 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

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 122 patients with high and intermediate-high risk endometrial cancer, those treated with a dose dense regimen of paclitaxel plus carboplatin showed a significantly higher three-year progression-free survival (79.5%) compared to those on the standard three-weekly protocol (57.4%).

The dose dense protocol also resulted in fewer progression events and distant metastases, along with improved overall survival in advanced stage cases, while experiencing fewer complaints of musculoskeletal pain compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Kogan, L., Laskov, I., Amajoud, Z., et al.[2022]

In a randomized phase II trial involving 349 patients with advanced endometrial cancer, the addition of novel agents to standard therapy (paclitaxel and carboplatin) did not significantly improve progression-free survival (PFS) compared to historical controls.

However, the combination of paclitaxel, carboplatin, and bevacizumab showed a significant increase in overall survival (OS) compared to controls, indicating that while PFS was not enhanced, the treatment may still offer long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Aghajanian, C., Filiaci, V., Dizon, DS., et al.[2023]

In a phase II study involving 66 patients with advanced and recurrent endometrial carcinoma, the combination of carboplatin and paclitaxel achieved an overall response rate of 67%, indicating a promising efficacy compared to previous treatments.

Despite the encouraging response rates, the median response duration was only 14 months, and the main toxicities included hematologic issues and sensory neuropathy, highlighting the need for further research to improve long-term outcomes and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Sorbe, B., Andersson, H., Boman, K., et al.[2018]

In a study of 25 patients with stage I-II serous endometrial cancer, the combination of surgery, intravaginal radiation therapy (IVRT), and chemotherapy (carboplatin/paclitaxel) was well tolerated, with 88% completing all 6 cycles of chemotherapy and only 4% experiencing severe toxicity.

The treatment resulted in a high 5-year progression-free and overall survival rate of 88%, with no cases of vaginal recurrence reported, suggesting that this approach is effective for early-stage serous endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent carboplatin/paclitaxel and intravaginal radiation in surgical stage I-II serous endometrial cancer. Alektiar, KM., Makker, V., Abu-Rustum, NR., et al.[2021]

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. 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.

4. 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 ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT183754

Adjuvant carboplatin and paclitaxel chemotherapy followed ... Conclusions: Our data suggests that adjuvant carboplatin and paclitaxel, followed by RT, in high-risk endometrial cancer is safe and effective.

6. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9019849/

Patient Reported Outcomes for Cisplatin and Radiation ... Findings from this study showed that Cis-RT+CP did not improve relapse-free survival in stage III/IVA endometrial carcinoma, and the type and extent of ...

8. emjreviews.com emjreviews.com/oncology/interactive-article/fda-approves-imfinzi-plus-carboplatin-and-paclitaxel-for-certain-patients-with-endometrial-cancer/

FDA Approves IMFINZI Plus Carboplatin and Paclitaxel for ... Safety data for IMFINZI + CP are available for a total of 44 patients with advanced or recurrent dMMR endometrial cancer. Patients received ...