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

Trial Summary

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.

What data supports the effectiveness of the drug combination of paclitaxel and carboplatin for endometrial cancer?

Research shows that the combination of paclitaxel and carboplatin is active against endometrial tumors, with a 67% overall response rate in patients with advanced or recurrent endometrial cancer. This combination has shown improved response rates compared to previous treatments, although the duration of response and long-term survival rates remain areas for further improvement. ^{1 2 3 4 5}

Is the combination of radiation and chemotherapy with carboplatin and paclitaxel safe for humans?

Studies have shown that the combination of carboplatin and paclitaxel with radiation therapy has been evaluated for safety in various cancers, including lung, cervical, and endometrial cancer. These studies aimed to determine the safe dosage and identify any side effects, indicating that this treatment approach has been considered generally safe for humans, though side effects can occur. ^{6 7 8 9 10}

How is the treatment of radiation and chemotherapy with carboplatin and paclitaxel unique for endometrial cancer?

This treatment combines intensity-modulated radiation therapy (IMRT) with chemotherapy drugs carboplatin and paclitaxel, which is unique because it uses advanced radiation techniques to precisely target cancer cells while minimizing damage to surrounding healthy tissue, and combines it with chemotherapy to enhance the overall effectiveness against advanced or high-risk endometrial cancer. ^{1 2 7 11 12}

What is the purpose of this trial?

The purpose of this study is to find out whether short-course radiation therapy (1 week instead of the usual 5 weeks) with chemotherapy (carboplatin and paclitaxel) is practical (feasible), meaning that most participants are able to complete the treatment schedule.

Research Team

Kaled Alektair, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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 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]

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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Concomitant paclitaxel plus carboplatin and radiotherapy for high-risk or advanced endometrial cancer. [2018]

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

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. [2018]

6. China 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]. [2010]

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

Concurrent carboplatin/paclitaxel and intravaginal radiation in surgical stage I-II serous endometrial cancer. [2021]

8. England 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. [2020]

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

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

10. 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]

11. 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]

12. United States 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. [2018]