Trials / Recruiting
RecruitingNCT07198074
Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer
A Randomized Phase III Trial of Carboplatin, Paclitaxel, Pembrolizumab Versus Carboplatin, Paclitaxel, Bevacizumab Versus Carboplatin, Paclitaxel, Pembrolizumab, Bevacizumab in the Treatment of pMMR, TP53 Mutated Advanced or Recurrent Endometrial Cancer
- Status
- Recruiting
- Phase
- Phase 3
- Study type
- Interventional
- Enrollment
- 255 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- Female
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase III trial compares the effect of bevacizumab in combination with carboplatin, paclitaxel and pembrolizumab to the usual treatments of carboplatin and paclitaxel with or without pembrolizumab in treating patients with stage III, IVA or IVB mismatch repair protein proficient (pMMR) and TP53 mutated endometrial cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has come back after a period of improvement (recurrent). Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adding bevacizumab to the combination of carboplatin, paclitaxel and pembrolizumab may be more effective than the usual treatment combinations of carboplatin and paclitaxel with or without pembrolizumab in treating patients with advanced or recurrent pMMR and TP53 mutated endometrial cancer.
Detailed description
PRIMARY OBJECTIVE: I. To demonstrate that bevacizumab, an anti-VEGF antibody therapy, (or an anti-VEGF antibody biosimilar) in combination with carboplatin, paclitaxel, and pembrolizumab is superior to carboplatin, paclitaxel, and pembrolizumab (the control arm) or carboplatin, paclitaxel, and bevacizumab in prolonging progression-free survival (PFS) in patients with pMMR, TP53 mutated advanced stage (III or IV) or recurrent endometrial cancer. SECONDARY OBJECTIVES: I. To demonstrate that bevacizumab in combination with carboplatin, paclitaxel, and pembrolizumab is superior to carboplatin, paclitaxel, and pembrolizumab or carboplatin, paclitaxel, and bevacizumab in prolonging overall survival (OS) in patients with pMMR, TP53 mutated advanced stage (III or IV) or recurrent endometrial cancer. II. To examine the impact of the addition of bevacizumab in combination with carboplatin and paclitaxel or with carboplatin, paclitaxel, and pembrolizumab on PFS and OS based on type of p53 immunohistochemistry (IHC) aberrancy (over expression/cytoplasmic expression versus null \[complete absence of staining\]) and mutation type. III. To evaluate toxicity on treatment with bevacizumab when combined with carboplatin, paclitaxel, and/or pembrolizumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0. IV. To explore the anti-tumor activity in each treatment arm as assessed by objective response rate in the subset of patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1 (REFERENCE ARM): Patients receive paclitaxel intravenously (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 additional14 cycles. Additionally, patients undergo urine and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. ARM 2 (EXPERIMENTAL TRIPLET ARM): 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. ARM 3 (EXPERIMENTAL QUADRUPLET ARM): 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. After completion of study treatment, patients are followed every 3 months for 2 years then every 6 months for up to 3 years.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | Bevacizumab | Given IV |
| PROCEDURE | Biospecimen Collection | Undergo urine and blood sample collection |
| DRUG | Carboplatin | Given IV |
| PROCEDURE | Computed Tomography | Undergo CT |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| DRUG | Paclitaxel | Given IV |
| BIOLOGICAL | Pembrolizumab | Given IV |
Timeline
- Start date
- 2026-01-27
- Primary completion
- 2028-07-01
- Completion
- 2028-07-01
- First posted
- 2025-09-30
- Last updated
- 2026-04-13
Locations
108 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT07198074. Inclusion in this directory is not an endorsement.