Chemotherapy Combinations for Endometrial Cancer

Recruiting at 268 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Bevacizumab, Temsirolimus

Disqualifiers: Other malignancies, Cardiovascular disease, CNS disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

349 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase II trial studies paclitaxel, carboplatin, and bevacizumab or paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, and bevacizumab to see how well they work in treating patients with stage III, stage IV, or recurrent endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which treatment regimen is most effective in treating patients with endometrial cancer.

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

The trial does not specify if you need to stop taking your current medications. However, you must not have received prior chemotherapy or targeted therapy for endometrial cancer, and any prior hormonal therapy must be stopped at least one week before starting the study.

Is the chemotherapy combination of paclitaxel and carboplatin safe for treating endometrial cancer?

Research shows that the combination of paclitaxel and carboplatin has been studied for safety in treating advanced or recurrent endometrial cancer. These studies evaluated the treatment's toxicity (side effects) and found it generally safe for use in humans, although specific side effects were not detailed. ^{1 2 3 4 5}

What makes the chemotherapy combination for endometrial cancer unique?

This treatment is unique because it combines multiple drugs, including bevacizumab (which targets blood vessel growth in tumors) and temsirolimus (an mTOR inhibitor that blocks cancer cell growth), with standard chemotherapy agents like carboplatin and paclitaxel, offering a novel approach for advanced or recurrent endometrial cancer. ^{5 6 7 8 9}

What data supports the effectiveness of the drug combination including Bevacizumab, Carboplatin, and Paclitaxel for endometrial cancer?

Research shows that adding Bevacizumab to Paclitaxel and Carboplatin can be effective for patients with advanced or recurrent endometrial cancer, as it was evaluated in a study focusing on this combination's efficacy. ^{1 3 4 5 10}

Who Is on the Research Team?

Carol Aghajanian

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced (stage III/IV) or recurrent endometrial cancer. Eligible participants may have had hormonal therapy but must not have received chemotherapy, targeted therapy, or radiation outside of specific criteria. They should have a certain level of blood cells and organ function, no serious wounds or bleeding risks, controlled seizures if present, stable heart conditions without recent severe events, and no known allergies to certain biologic drugs.

Inclusion Criteria

Informed consent and authorization required

Bilirubin <= 1.5 x ULN (CTCAE v3.0 grade 1)

SGOT and SGPT <= 2.5 x ULN (CTCAE v3.0 grade 1)

Exclusion Criteria

Known hypersensitivity to specific products exclusion criteria specified

Pregnant or nursing exclusion criteria specified

I have had chemotherapy for a tumor in my abdomen or pelvis in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy and monoclonal antibodies in one of three treatment arms, repeated every 21 days for 6 courses

18 weeks

6 visits (in-person)

Maintenance Therapy

Participants receive maintenance therapy with bevacizumab or temsirolimus every 21 days in the absence of disease progression or unacceptable toxicity

Variable, based on disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Ixabepilone
• Paclitaxel
• Temsirolimus

Trial Overview The study compares three treatment combinations: Paclitaxel with Carboplatin and Bevacizumab; Paclitaxel with Carboplatin and Temsirolimus; Ixabepilone with Carboplatin and Bevacizumab. It aims to find out which regimen is most effective in stopping tumor growth by killing the cells or preventing them from dividing.

How Is the Trial Designed?

Group I: Arm III (ixabepilone, carboplatin, bevacizumab) Experimental Treatment 4 Interventions

Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (paclitaxel, carboplatin, temsirolimus) Experimental Treatment 4 Interventions

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (paclitaxel, carboplatin, bevacizumab) Experimental Treatment 4 Interventions

Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a study involving 27 patients with advanced or recurrent endometrial carcinoma, the combination of bevacizumab with paclitaxel and carboplatin showed a high response rate of 82.8% in first-line therapy, indicating its efficacy in treating this cancer.

The median progression-free survival was 20 months and median overall survival was 56 months, suggesting that this treatment regimen can significantly extend the lives of patients with advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. Rose, PG., Ali, S., Moslemi-Kebria, M., et al.[2018]

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 involving 90 patients with advanced or recurrent endometrial carcinoma, three combination therapies (docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin) showed tumor response rates of 51.7%, 48.3%, and 60.0%, respectively, indicating that all regimens are potentially effective.

The safety profiles of the treatments were similar, with high rates of grade 3/4 neutropenia observed across all groups, suggesting that while these therapies are effective, they also carry significant risks of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Nomura, H., Aoki, D., Takahashi, F., et al.[2020]

In a study of 48 patients with high-risk stage III and IV endometrial cancer, the combination of paclitaxel and carboplatin (TC) after complete tumor resection resulted in a 3-year overall survival rate of 56% and a median overall survival of 47 months.

The treatment was well tolerated, with 90% of patients completing all planned cycles, and a median time to disease progression of 13 months, indicating that TC is an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Sovak, MA., Hensley, ML., Dupont, J., 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]

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 phase III study involving 496 women with advanced endometrial cancer, ixabepilone did not improve overall survival compared to standard chemotherapy (doxorubicin or paclitaxel), leading to the study's discontinuation based on interim results.

The safety profiles of ixabepilone and the control treatments were comparable, indicating that while ixabepilone was not more effective, it also did not present additional safety concerns compared to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. McMeekin, S., Dizon, D., Barter, J., 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. [2018]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). [2020]

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

Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. [2015]

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

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

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

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

7. Turkey pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bevacizumab-Combined Chemotherapy for Advanced and Recurrent Endometrial Cancer: A Systematic Review and Meta-analysis. [2023]

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

Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings. [2023]

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

Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. [2015]