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NCT07198074From ClinicalTrials.govRecruiting

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

  • Advanced Endometrial Carcinoma
  • Recurrent Endometrial Carcinoma

At a glance

Phase
Phase 3
Study type
Interventional
Sponsor
National Cancer Institute (NCI)
Enrolment target
255
Started
27 January 2026
Main results due
1 July 2028
Study sites
294
Registry updated
29 September 2026

Can you take part?

  • Aged 18 years and over.
  • Women only.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full eligibility criteria
Inclusion Criteria:

* Documentation of disease:

  * Stage III and stage IVA endometrial cancers (with measurable disease),
  * Stage IVB endometrial cancer (with or without measurable disease), or
  * Recurrent endometrial cancer (with or without measurable disease)
* In patients with measurable disease, lesions will be defined and monitored by RECIST 1.1. Measurable disease (RECIST 1.1) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI
* Histologic confirmation of the original primary tumor is required (submission of pathology report\[s\] is required). Patients with the following histologic types are eligible: endometrioid, serous, dedifferentiated/undifferentiated, clear cell, mixed epithelial, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.)
* Patients must have:

  * Tumoral mismatch repair proficient (pMMR) disease as assessed by immunohistochemistry (IHC) AND
  * P53 IHC with aberrant staining pattern (aberrant p53 expression is consistent with mutant TP53). TP53 mutation by next-generation sequencing will also be accepted
* A pathology report demonstrating results of institutional MMR IHC and p53 IHC and/or TP53 by next-generation sequencing
* Patients may have received:

  * NO prior chemotherapy for treatment of endometrial cancer OR
  * Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\]) provided adjuvant chemotherapy was completed ≥ 12 months prior to registration
* Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to registration. For patients with recent radiation, they must have RECIST-evaluable disease outside of the radiation field and have recovered their marrow function
* Patients may have received prior hormonal (endocrine) therapy. All hormonal (endocrine) therapy must have been completed at least 1 week prior to registration
* NO prior pembrolizumab (or other anti-PD1, anti-PDL1 or anti-CTLA4 therapy) or bevacizumab (or other antiangiogenic therapy)
* Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dl
* Creatinine clearance (CrCl) of ≥ 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* No active infection requiring parenteral antibiotics
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No clinically significant bleeding within 28 days prior to registration
* No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg
* No major surgery within 28 days of initiation of bevacizumab
* No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease

  * Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
  * Topical or inhaled steroids are allowed
  * Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), and anti-thyroid antibodies should be evaluated with the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* No history of stem cell or solid organ transplant
* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)

What this study is about

In the sponsor’s own words, from the registry.

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.

Study sites(294)

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, United States

    Recruiting

  • Alaska Women's Cancer Care

    Anchorage, Alaska, United States

    Recruiting

  • Cancer Center at Saint Joseph's

    Phoenix, Arizona, United States

    Recruiting

  • Banner University Medical Center - Tucson

    Tucson, Arizona, United States

    Recruiting

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, United States

    Recruiting

  • Highlands Oncology Group - Fayetteville

    Fayetteville, Arkansas, United States

    Recruiting

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, United States

    Recruiting

  • Highlands Oncology Group - Rogers

    Rogers, Arkansas, United States

    Recruiting

  • Highlands Oncology Group

    Springdale, Arkansas, United States

    Recruiting

  • Mercy Cancer Center - Carmichael

    Carmichael, California, United States

    Recruiting

  • Mercy San Juan Medical Center

    Carmichael, California, United States

    Recruiting

  • Kaiser Permanente Dublin

    Dublin, California, United States

    Recruiting

  • Mercy Cancer Center - Elk Grove

    Elk Grove, California, United States

    Recruiting

  • Kaiser Permanente-Fremont

    Fremont, California, United States

    Recruiting

  • Kaiser Permanente Fresno Orchard Plaza

    Fresno, California, United States

    Recruiting

  • Los Angeles General Medical Center

    Los Angeles, California, United States

    Recruiting

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, United States

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, United States

    Recruiting

  • Kaiser Permanente- Modesto MOB II

    Modesto, California, United States

    Recruiting

  • Kaiser Permanente-Oakland

    Oakland, California, United States

    Recruiting

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, United States

    Recruiting

  • Eisenhower Medical Center

    Rancho Mirage, California, United States

    Recruiting

  • Mercy Cancer Center - Rocklin

    Rocklin, California, United States

    Recruiting

  • Kaiser Permanente-Roseville

    Roseville, California, United States

    Recruiting

  • Kaiser Permanente Downtown Commons

    Sacramento, California, United States

    Recruiting

  • Mercy Cancer Center - Sacramento

    Sacramento, California, United States

    Recruiting

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, United States

    Recruiting

  • Kaiser Permanente-South Sacramento

    Sacramento, California, United States

    Recruiting

  • Kaiser Permanente-San Francisco

    San Francisco, California, United States

    Recruiting

  • Kaiser Permanente-Santa Teresa-San Jose

    San Jose, California, United States

    Recruiting

  • Kaiser Permanente San Leandro

    San Leandro, California, United States

    Recruiting

  • Kaiser San Rafael-Gallinas

    San Rafael, California, United States

    Recruiting

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, United States

    Recruiting

  • Kaiser Permanente-Santa Rosa

    Santa Rosa, California, United States

    Recruiting

  • Kaiser Permanente-South San Francisco

    South San Francisco, California, United States

    Recruiting

  • Kaiser Permanente-Vallejo

    Vallejo, California, United States

    Recruiting

  • Kaiser Permanente-Walnut Creek

    Walnut Creek, California, United States

    Recruiting

  • Woodland Memorial Hospital

    Woodland, California, United States

    Recruiting

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, United States

    Recruiting

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, United States

    Recruiting

  • Memorial Hospital North

    Colorado Springs, Colorado, United States

    Recruiting

  • Poudre Valley Hospital

    Fort Collins, Colorado, United States

    Recruiting

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, United States

    Recruiting

  • UCHealth Greeley Hospital

    Greeley, Colorado, United States

    Recruiting

  • UCHealth Highlands Ranch Hospital

    Highlands Ranch, Colorado, United States

    Recruiting

  • Medical Center of the Rockies

    Loveland, Colorado, United States

    Recruiting

  • Hartford Hospital

    Hartford, Connecticut, United States

    Recruiting

  • Hartford HealthCare - Manchester

    Manchester, Connecticut, United States

    Recruiting

  • The Hospital of Central Connecticut

    New Britain, Connecticut, United States

    Recruiting

  • Beebe South Coastal Health Campus

    Millville, Delaware, United States

    Recruiting

  • Helen F Graham Cancer Center

    Newark, Delaware, United States

    Recruiting

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, United States

    Recruiting

  • Beebe Health Campus

    Rehoboth Beach, Delaware, United States

    Recruiting

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, United States

    Recruiting

  • Sarasota Memorial Hospital-Venice

    N. Venice, Florida, United States

    Recruiting

  • Florida Cancer Specialists - Sarasota Downtown

    Sarasota, Florida, United States

    Recruiting

  • FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery

    Sarasota, Florida, United States

    Recruiting

  • Sarasota Memorial Hospital

    Sarasota, Florida, United States

    Recruiting

  • Sarasota Memorial Health Care Center at University Parkway

    Sarasota, Florida, United States

    Recruiting

  • Florida Cancer Specialists - Venice Pinebrook

    Venice, Florida, United States

    Recruiting

Showing 60 of 294 sites — filter to narrow it down. 292 of the 294 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT07198074. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Comb | Trialion