Chemotherapy Combinations for Endometrial Cancer

Not currently recruiting at 276 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the most effective chemotherapy combination for advanced or recurring endometrial cancer. Researchers will test three different drug regimens, each using a mix of drugs such as paclitaxel, carboplatin, bevacizumab (Avastin), temsirolimus, or ixabepilone, which stop or slow tumor growth in various ways. The trial seeks participants with stage III or IV endometrial cancer, or cancer that has returned after treatment, who have not previously received chemotherapy for this cancer. 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 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of paclitaxel, carboplatin, and bevacizumab is generally well-tolerated by patients with endometrial cancer. Studies have found these drugs to be effective, with side effects that are usually manageable. However, some patients might experience higher blood pressure or fatigue.

For the combination of paclitaxel, carboplatin, and temsirolimus, previous patients have found it quite tolerable, though reports have noted severe fatigue and low platelet levels, which are crucial for blood clotting.

The combination of ixabepilone, carboplatin, and bevacizumab is also under study for safety. Like the other treatments, it is generally manageable, but some individuals might experience similar side effects, such as fatigue or increased blood pressure.

Overall, these treatments have been used in other types of cancer, suggesting a level of safety. However, individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they combine chemotherapy with targeted therapies that may enhance effectiveness. Unlike standard treatments that often rely solely on chemotherapy, these combinations include innovative drugs like bevacizumab and temsirolimus, which inhibit blood vessel growth and target specific cancer cell pathways. The addition of ixabepilone offers a unique mechanism by stabilizing microtubules, potentially increasing cancer cell death. These novel combinations could lead to improved outcomes by attacking the cancer from multiple angles, offering hope for better control of the disease.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

This trial will evaluate different chemotherapy combinations for endometrial cancer. Research has shown that a combination of paclitaxel, carboplatin, and bevacizumab, which participants in Arm I may receive, can be effective in treating endometrial cancer. In one study, 82.8% of patients responded positively, with some experiencing complete tumor shrinkage. This suggests that this combination can effectively target and slow tumor growth.

Participants in Arm II will receive paclitaxel, carboplatin, and temsirolimus. Early data indicates that temsirolimus might block enzymes necessary for tumor growth. However, more research is needed to confirm its effectiveness.

For those in Arm III, the combination of ixabepilone, carboplatin, and bevacizumab has shown significant benefits for endometrial cancer. Studies have demonstrated that adding bevacizumab increased response rates to 74.4% in some cases, suggesting it may enhance treatment effectiveness. ^{1 2 3 4 6}

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 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 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 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 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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8909221/

Efficacy and Safety of Bevacizumab-Combined ... According to recent randomized-controlled trials (RCTs), the combination of PC with bevacizumab showed significant benefits in endometrial cancer (3, 4).

2. balkanmedicaljournal.org balkanmedicaljournal.org/pdf.php?&id=2280

Efficacy and Safety of Bevacizumab-Combined ... According to recent randomized-controlled trials (RCTs), the combination of. PC with bevacizumab showed significant benefits in endometrial cancer (3, 4).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00977574

Study Details | NCT00977574 | Paclitaxel, Carboplatin, and ... 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29804638/

A phase II study of frontline paclitaxel/carboplatin ... - PubMed Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating ...

5. onclive.com onclive.com/view/targeted-therapy-immunotherapy-are-replacing-chemotherapy-in-endometrial-cancer

Targeted Therapy, Immunotherapy Are Replacing ... However, the addition of bevacizumab did improve ORR (74.4% vs 53.1%), which may be enough to show that the combination should be explored ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1040842824002981

First-line treatments for advanced or recurrent endometrial ... Median progression-free survival was reported in 28 trials (range, 1.9–18.8 months), median overall survival in 26 trials with mature data (range, 6.9–41 months) ...