Bevacizumab + Chemotherapy + Immunotherapy for Endometrial Cancer

Recruiting at 26 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-PD1, Anti-PDL1, Anti-CTLA4, Antiangiogenic

Disqualifiers: Autoimmune disease, Uncontrolled hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 5

Duration: 18-30 weeks

255 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medicines for advanced or recurring endometrial cancer. Researchers are investigating whether adding bevacizumab, a drug that inhibits tumor blood vessel growth, to the standard chemotherapy (carboplatin and paclitaxel) and immunotherapy (pembrolizumab) can enhance cancer treatment. The trial includes three different treatment groups to determine the most effective approach. Individuals with advanced or recurring endometrial cancer that exhibits certain genetic traits and who have not previously used specific cancer drugs may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

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 pembrolizumab is generally well-tolerated for treating advanced endometrial cancer. In earlier studies, patients experienced longer periods without cancer progression compared to those who received only chemotherapy. This suggests that adding pembrolizumab can enhance treatment outcomes without causing many additional side effects.

For the combination of paclitaxel, carboplatin, and bevacizumab, studies have found it to be a suitable treatment option. Patients tolerated it well, although some cases showed a higher risk of developing febrile neutropenia, a fever with a low white blood cell count. Despite this, the combination has shown promise in extending the time patients live without cancer progression.

When bevacizumab is added to paclitaxel, carboplatin, and pembrolizumab, patients have tolerated it well. This treatment combination may be more effective than standard chemotherapy treatments. Overall, these treatments are considered safe, with most side effects being manageable with medical care. ^{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 powerful therapies that work in different ways to attack the cancer. Bevacizumab, a key player in some treatment arms, is an anti-VEGF therapy that blocks the blood supply tumors need to grow, making it different from traditional chemotherapy. Additionally, pembrolizumab is an immunotherapy that helps the immune system recognize and fight cancer cells, offering a promising approach alongside chemotherapy. This combination approach has the potential to enhance treatment effectiveness and provide new hope for patients with endometrial cancer.

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

Research has shown that adding pembrolizumab to chemotherapy with carboplatin and paclitaxel can improve outcomes for endometrial cancer patients. In earlier studies, patients experienced a median progression-free survival of 13.1 months with pembrolizumab, meaning the cancer did not worsen during that period, compared to 8.7 months without it. In this trial, one group will receive paclitaxel, carboplatin, and pembrolizumab. Bevacizumab, another drug in the study, stops new blood vessels from forming, which can help slow tumor growth. When combined with paclitaxel and carboplatin, bevacizumab has shown a median progression-free survival of 20 months in some cases. Another group in this trial will receive paclitaxel, carboplatin, and bevacizumab. The trial also explores whether adding both pembrolizumab and bevacizumab to chemotherapy enhances treatment effectiveness, which is being tested in a separate group. ^{6 7 8 9 10}

Who Is on the Research Team?

Amanda N Fader

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with advanced or recurrent endometrial cancer that's pMMR and TP53 mutated. Eligible participants may have had prior hormonal therapy, radiation, or adjuvant chemotherapy (if completed over a year ago). They should have measurable disease by certain criteria and no previous chemo specifically for endometrial cancer.

Inclusion Criteria

My condition is either stage IVB endometrial cancer or recurrent endometrial cancer.

My endometrial cancer is at stage III or IVA and can be measured.

I finished any hormone therapy at least a week ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel, carboplatin, and pembrolizumab with or without bevacizumab every 3 weeks for 6-10 cycles

18-30 weeks

1 visit every 3 weeks (in-person)

Maintenance

Participants may continue to receive maintenance pembrolizumab and/or bevacizumab after the combination phase

up to 84 weeks

1 visit every 3-6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

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

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview

The study tests adding Bevacizumab to the usual treatment of Carboplatin and Paclitaxel, with or without Pembrolizumab. It aims to see if this combination is more effective in treating stage III/IVB or recurrent pMMR, TP53 mutated endometrial cancer than the standard treatments alone.

How Is the Trial Designed?

Group I: Arm 3 (paclitaxel, carboplatin, pembrolizumab, bevacizumab) Experimental Treatment 7 Interventions

Patients receive paclitaxel IV over 3 hours, carboplatin IV, pembrolizumab IV over 30 minutes, and bevacizumab IV or anti-VEGF antibody biosimilar on day 1 of each cycle. Cycles repeat every 3 weeks for up to 6-10 cycles in the absence of disease progression or unacceptable toxicity. Starting 3 weeks after last combination phase cycle, patients may continue to receive maintenance pembrolizumab IV over 30 minutes every 6 weeks for up to an additional 14 cycles and bevacizumab IV every 3 weeks for up to an additional 28 doses. Additionally, patients undergo urine and blood sample collection and CT or MRI throughout the study.

Group II: Arm 2 (paclitaxel, carboplatin, bevacizumab) Experimental Treatment 6 Interventions

Patients receive paclitaxel IV over 3 hours, carboplatin IV, and bevacizumab IV or anti-VEGF antibody biosimilar on day 1 of each cycle. Cycles repeat every 3 weeks for up to 6-10 cycles in the absence of disease progression or unacceptable toxicity. Starting 3 weeks after last combination phase cycle, patients may continue to receive maintenance bevacizumab IV on day 1 of each cycle. Treatment repeats every 3 weeks for up to an additional 28 doses. Additionally, patients undergo urine and blood sample collection and CT or MRI throughout the study.

Group III: Arm 1 (paclitaxel, carboplatin, pembrolizumab) Active Control 6 Interventions

Patients receive paclitaxel IV over 3 hours, carboplatin IV and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 6-10 cycles in the absence of disease progression or unacceptable toxicity. Starting 3 weeks after last combination phase cycle, patients may continue to receive maintenance pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to an additional 14 cycles. Additionally, patients undergo urine and blood sample collection and CT or MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28187088/

Paclitaxel, Carboplatin, and Bevacizumab in Advanced ...

Collectively, the median progression-free survival was 20 months, and median overall survival was 56 months. Among 29 patients with measurable disease, the ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1048891X24075571

Paclitaxel, Carboplatin, and Bevacizumab in Advanced ...

The aim of this study was to evaluate the efficacy of adding bevacizumab to paclitaxel and carboplatin and as maintenance in a larger cohort of patients.

3.

gynecologiconcology-online.net

gynecologiconcology-online.net/article/S0090-8258(19)31596-3/abstract

MITO END-2 - A randomized phase II trial

Bevacizumab combined with chemotherapy does not increase PFS in comparison to chemotherapy in recurrent endometrial cancer. •. Cardiovascular events were more ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)00721-X/fulltext

Overall survival in patients with endometrial cancer treated ...

An improvement of 13.9 months in median PFS2 was observed in patients receiving dostarlimab plus carboplatin–paclitaxel (median PFS2 of 32.3 ...

5.

international-journal-of-gynecological-cancer.com

international-journal-of-gynecological-cancer.com/article/S1048-891X(25)00181-1/pdf

Real-world treatment patterns and clinical outcomes in ...

The Endometrial Cancer Health Outcomes-Europe (ECHO-EU) study described treatment patterns and clinical outcomes in advanced/recurrent ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7676887/

Carboplatin and Paclitaxel for Advanced Endometrial Cancer

The data safety monitoring board reported an increase in febrile neutropenia ... carboplatin/bevacizumab in advanced/recurrent endometrial cancer.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00977574

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

Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study.

8.

cancernetwork.com

cancernetwork.com/view/adding-bevacizumab-chemotherapy-improves-pfs-endometrial-cancer

Adding Bevacizumab to Chemotherapy Improves PFS in ...

The addition of bevacizumab to carboplatin/paclitaxel chemotherapy significantly increases progression-free survival (PFS) in advanced/recurrent endometrial ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0090825822002529

Paclitaxel-carboplatin and bevacizumab combination with ...

Conclusions. Paclitaxel–carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

10.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.5502

Randomized phase II trial of carboplatin-paclitaxel (CP) ...

The antiangiogenic drug Bevacizumab (B) has reported activity in AEC with response rates ranging from 13 to 22% and 6-month disease control up ...