Chemotherapy + IMPT for Endometrial Cancer

No longer recruiting at 3 trial locations

Overseen By Ermiece Straub, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must be taking: Chemotherapy

Disqualifiers: Leiomyosarcoma, Recurrent cancer, Prior RT, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for patients with advanced endometrial cancer. It combines the chemotherapy drugs carboplatin and paclitaxel with a special type of radiation therapy called Intensity Modulated Proton Therapy (IMPT). The goal is to determine if this new approach is as effective and manageable as past treatments. It suits patients who have had surgery for advanced endometrial cancer and need additional treatment, but not those with certain heart issues or prior cancer treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

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 has shown that the drugs carboplatin and paclitaxel are generally well-tolerated, particularly for ovarian and endometrial cancers. They are often used together because they typically do not require additional medications to manage side effects, making them a convenient choice for many patients.

Studies have also found that Intensity Modulated Proton Therapy (IMPT) is safe for treating uterine cancers. Patients usually experience only mild side effects, such as less diarrhea compared to other radiation treatments. This makes IMPT a promising option for those concerned about treatment discomfort.

In summary, both the chemotherapy drugs and IMPT have a history of being well-tolerated in similar situations, offering reassurance about their safety for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with IMPT (Intensity Modulated Proton Therapy) for treating endometrial cancer because it offers a more targeted approach. Unlike traditional radiation therapies that can affect surrounding healthy tissues, IMPT precisely targets cancer cells, potentially reducing harmful side effects. This combination with carboplatin and paclitaxel, which are effective chemotherapy agents, might enhance the overall treatment efficacy by attacking the cancer on multiple fronts. The hope is that this dual approach could improve outcomes for patients compared to current 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 effectively treats advanced endometrial cancer. Studies have found that patients with advanced or recurrent cancer lived longer, with an average survival time of 37 to 41 months, and the cancer did not worsen for about 13 to 14 months.

In this trial, participants will receive concurrent chemoradiation with carboplatin and paclitaxel, combined with Intensity Modulated Proton Therapy (IMPT). IMPT has shown promise in reducing side effects compared to traditional radiation treatments, potentially causing fewer digestive issues and helping maintain sexual function after treatment. Together, these treatments offer a potentially effective way to manage advanced endometrial cancer that has spread locally. ^{1 2 6 7 8}

Who Is on the Research Team?

Pranshu Mohindra, MD

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced endometrial cancer who've had a hysterectomy and possibly other related surgeries. It's open to those with certain stages of cancer, including stage IVA or IA-III if it's clear cell, serous papillary carcinoma, or carcinosarcoma. Participants need normal organ function and no history of heart issues in the past 3 months. They can't have had prior chemotherapy for any cancer.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I am stage IVA and advised to get pelvic radiation and chemotherapy.

Absolute neutrophil count (ANC) ≥ 1000/mcl

Exclusion Criteria

I have recurrent endometrial cancer needing high dose radiotherapy or have had chemotherapy before.

I have significant nodal disease in my pelvis or para-aortic area that wasn't removed and needs a higher radiation dose.

I have not had radiation in the pelvic/abdominal area or chemotherapy that would interfere with this treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Chemoradiation

Participants receive concurrent carboplatin and paclitaxel chemotherapy with Intensity Modulated Proton Therapy (IMPT)

5-6 weeks

Weekly visits during radiation treatment

Chemotherapy

Participants complete full 6 cycles of chemotherapy with carboplatin and paclitaxel

18 weeks

Once every 21 days

Follow-up

Participants are monitored for late GI and urinary toxicity

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin and Paclitaxel
• Pelvic IMPT (Intensity Modulated Proton Therapy)

Trial Overview The UPPROACH study tests whether combining Intensity Modulated Proton Beam Therapy (IMPT) with chemotherapy (carboplatin and paclitaxel) after surgery is as good at keeping patients on treatment as previous methods were. This phase 2 trial focuses on compliance rates compared to historical data from the GOG 258 study.

How Is the Trial Designed?

Group I: Concurrent chemoradiation Experimental Treatment 2 Interventions

Concurrent carboplatin and paclitaxel and IMPT (Intensity Modulated Proton Therapy)

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

Approved in European Union as Carboplatin and Paclitaxel for:

• Lung cancer
• Ovarian cancer
• Womb cancer
• Cervical cancer

Approved in United States as Carboplatin and Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Cervical cancer
• Endometrial cancer
• Thymoma or thymic carcinoma

Approved in Canada as Carboplatin and Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Breast cancer

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

The combination of triweekly carboplatin and weekly paclitaxel is feasible and effective for treating women with advanced or recurrent endometrial cancer, with 78% of patients completing at least 3 cycles of therapy.

Among patients with measurable disease, 87% showed a positive response to treatment, and quality of life scores significantly improved after 3 cycles, indicating both efficacy and a positive impact on patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial). Ito, K., Tsubamoto, H., Itani, Y., 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]

A patient with recurrent metastatic endometrial cancer achieved complete remission after 8 months of treatment with a combination of paclitaxel and carboplatin, which has lasted for 22 months.

This case suggests that the paclitaxel and carboplatin regimen could be a promising treatment option for patients with recurrent endometrial cancer, especially when other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged remission of endometrial cancer with paclitaxel and carboplatin. Vasuratna, A., Kudelka, AP., Edwards, CL., et al.[2019]

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 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 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]

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 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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10373231/

Looking Beyond Carboplatin and Paclitaxel for the ... Median OS was 37 months and 41 months, respectively (HR: 1.002; 90% CI: 0.9 to 1.12); median progression-free survival (PFS) was 13 months and 14 months, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24088479

Weekly Paclitaxel-Carboplatin Regimen in Patients With ... Paclitaxel/carboplatin weekly seems effective, however, with a considerable hematologic toxicity. Larger trials are needed to confirm these data.

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825808006707

Reuse of carboplatin and paclitaxel in patients with ... Carboplatin and paclitaxel was reused in 31 (60% of 52 retreated with chemotherapy or 29% of the total cohort of 111). There was no statistically significant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00942357

Study Details | NCT00942357 | Carboplatin and Paclitaxel ... This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating ...

7. hemonc.org hemonc.org/wiki/Endometrial_cancer

Endometrial cancer Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial ...

8. chemoexperts.com chemoexperts.com/carboplatin-paclitaxel-uterine.html

Treatment Name: Carboplatin + Paclitaxel (Carbo/Taxol®) If the disease is metastatic, it may be given to decrease the symptoms of uterine cancer and prolong life.