Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

RECRUITING

NCT07198074

PHASE3

Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Official title: 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

Key Details

Gender

FEMALE

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

255

Start Date

2026-01-27

Completion Date

2028-07-01

Last Updated

2026-11-03

Healthy Volunteers

Conditions

Advanced Endometrial Carcinoma Recurrent Endometrial Carcinoma

Interventions

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

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)

Locations (305)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Cancer Center at Saint Joseph's

Phoenix, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Highlands Oncology Group - Rogers

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

Mercy Cancer Center - Carmichael

Carmichael, California, United States

Mercy San Juan Medical Center

Carmichael, California, United States

Kaiser Permanente Dublin

Dublin, California, United States

Mercy Cancer Center - Elk Grove

Elk Grove, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Kaiser Permanente Fresno Orchard Plaza

Fresno, California, United States

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Kaiser Permanente- Modesto MOB II

Modesto, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Eisenhower Medical Center

Rancho Mirage, California, United States

Mercy Cancer Center - Rocklin

Rocklin, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

Kaiser Permanente Downtown Commons

Sacramento, California, United States

Mercy Cancer Center - Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Kaiser San Rafael-Gallinas

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

Woodland Memorial Hospital

Woodland, California, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado, United States

UCHealth Greeley Hospital

Greeley, Colorado, United States

UCHealth Highlands Ranch Hospital

Highlands Ranch, Colorado, United States

Medical Center of the Rockies

Loveland, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

Hartford HealthCare - Manchester

Manchester, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Beebe South Coastal Health Campus

Millville, Delaware, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Beebe Health Campus

Rehoboth Beach, Delaware, United States

MedStar Washington Hospital Center

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

Sarasota Memorial Hospital-Venice

N. Venice, Florida, United States

Florida Cancer Specialists - Sarasota Downtown

Sarasota, Florida, United States

FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery

Sarasota, Florida, United States

Sarasota Memorial Hospital

Sarasota, Florida, United States

Sarasota Memorial Health Care Center at University Parkway

Sarasota, Florida, United States

Florida Cancer Specialists - Venice Pinebrook

Venice, Florida, United States

Grady Health System

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Augusta University Medical Center

Augusta, Georgia, United States

Emory Decatur Hospital

Decatur, Georgia, United States

Hawaii Cancer Care Inc - Waterfront Plaza