Chemotherapy + IMPT for Endometrial Cancer

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase 2 study with the primary objective of testing treatment compliance of Upfront Intensity Modulated Proton Beam Therapy (IMPT) and Concurrent Chemotherapy (UPPROACH) for Post-operative Treatment in Loco-regionally Advanced Endometrial Cancer is non-inferior to the historic compliance rate of the chemoradiation arm of GOG 258 study

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.

What data supports the effectiveness of the treatment for endometrial cancer?

Research shows that the combination of carboplatin and paclitaxel is effective in reducing tumor size in patients with advanced or recurrent endometrial cancer, with a significant number of patients experiencing partial responses. This combination is considered a standard initial therapy for advanced endometrial cancer, demonstrating activity against tumors with acceptable levels of side effects. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs Carboplatin and Paclitaxel, along with Intensity Modulated Proton Therapy, generally safe for humans?

The combination of Carboplatin and Paclitaxel has been studied for endometrial cancer and is generally considered to have acceptable levels of toxicity, though some patients experienced significant side effects like hematologic toxicity (blood-related side effects) and neuropathy (nerve damage). Intensity Modulated Proton Therapy has been evaluated in combination with these drugs for cervical cancer, focusing on determining safe dosage levels. ^{1 2 3 4 6}

How does the treatment of Chemotherapy + IMPT for Endometrial Cancer differ from other treatments?

This treatment is unique because it combines chemotherapy drugs, carboplatin and paclitaxel, with Intensity Modulated Proton Therapy (IMPT), a type of radiation therapy that uses protons to precisely target tumors, potentially reducing damage to surrounding healthy tissues compared to traditional radiation. ^{1 2 7 8 9}

Research Team

Pranshu Mohindra, MD

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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]

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 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]

References

1. 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]

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

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

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

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

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

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

6. 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]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Prolonged remission of endometrial cancer with paclitaxel and carboplatin. [2019]

9. United States 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). [2015]