A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
Trial Status: Active
Endometrial cancer accounts for greater than 90 percent (%) of all uterine cancer. The majority of participants with endometrial cancer are diagnosed in early stages (Stage I or II) and receive surgery with curative intent; however, approximately 20% are diagnosed with advanced or metastatic disease (Stage III or IV) for which a surgical cure is not possible. Paclitaxel in combination with carboplatin has been shown to be efficacious against a variety of different tumor types, including non-small-cell-lung-carcinoma (NSCLC), ovarian cancer, endometrial cancer, and head and neck cancer. This study will evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel, the standard of care for participants with recurrent or primary advanced endometrial cancer. This study consists of a Screening Period, Treatment Period, an End of Treatment (EOT) Visit, a Safety Follow-up Visit, and a Survival Assessment Period. Participants will be randomized in a 1:1 ratio to receive either dostarlimab plus carboplatin paclitaxel or placebo plus carboplatin-paclitaxel.
- Female participant is at least 18 years of age, able to understand the study procedures, and agrees to participate in the study by providing written informed consent.
- Participant has histologically or cytologically proven endometrial cancer with recurrent or advanced disease.
- Participant must provide adequate tumor tissue sample at Screening for microsatellite instability (MSI) status testing.
- Participant must have primary Stage III or Stage IV disease or first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone or in combination and meet at least one of the following criteria; a) Participant has primary Stage IIIA to IIIC1 disease with presence of evaluable or measurable disease per RECIST v.1.1 based on Investigator's assessment. Lesions that are equivocal or can be representative of postoperational change should be biopsied and confirmed for the presence of tumor; b) Participant has primary Stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histology (containing >= 10% carcinosarcoma, clear cell, or serous histology) regardless of presence of evaluable or measurable disease on imaging; c) Participant has primary Stage IIIC2 or Stage IV disease; d) Participant has first recurrent disease and is chemotherapy naïve; e) Participant has received prior neo-adjuvant/adjuvant systemic chemotherapy and had a recurrence or PD >= 6 months after completing treatment (first recurrence only).
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participant has adequate organ function as follows: a) Absolute neutrophil count >= 1,500 cells/micro Liters (mcL); b) Platelets >= 100,000 cells/mcL; c) Hemoglobin >= 9 grams per deciliter (g/dL) or >= 5.6 millimoles per Liter (mmol/L); d) Serum creatinine <= 1.5× upper limit of normal (ULN) or calculated creatinine clearance >= 50 milliliter per minute (mL/min) using the Cockcroft-Gault equation for participants with creatinine levels > 1.5× institutional ULN; e) Total bilirubin <= 1.5× ULN and direct bilirubin <= 1× ULN; f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5× ULN unless liver metastases are present, in which case they must be <= 5× ULN; g) International normalized ratio or prothrombin time (PT) <=1.5× ULN and activated partial thromboplastin time <=1.5× ULN. Participants receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants.
- Participant must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of nonchildbearing potential. Nonchildbearing potential is defined as follows: a) Participant is >= 45 years of age and has not had menses for > 1 year; b) A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrheic for < 2 years without a hysterectomy and oophorectomy; c) Posthysterectomy, postbilateral oophorectomy, or posttubal ligation.
- Participants of childbearing potential must agree to use 2 adequate methods of contraception with their partners starting with the screening visit through 180 days after the last dose of study treatment.
- Participant has received neo-adjuvant/adjuvant systemic chemotherapy for primary Stage III or IV disease and: a) has not had a recurrence or PD prior to entering the study OR b) has had a recurrence or PD within 6 months of completing chemotherapy treatment prior to entering the study.
- Participant has had at least 1 recurrence of endometrial cancer.
- Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Participant has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy, or immunotherapy) within 21 days or < 5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter.
- Participant has a concomitant malignancy, or participant has a prior non-endometrial invasive malignancy who has been disease-free for < 3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
- Participant has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
- Participant has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
- Participant has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] is detected).
- Participant has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (eg, thyroid hormone or insulin).
- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant has not recovered (ie, to Grade <= 1 or to Baseline) from cytotoxic therapy induced AEs.
- Participant has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
- Participant has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab components or excipients.
- Participant is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, noninfectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
- Participant is pregnant or breastfeeding or is expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
Stanford Cancer Institute Palo Alto
University of Miami Miller School of Medicine-Sylvester Cancer Center
Indiana University / Melvin and Bren Simon Cancer Center
Contact: Seth Burns
University of Iowa / Holden Comprehensive Cancer Center
University of Kentucky / Markey Cancer Center
Massachusetts General Hospital Cancer Center
Wayne State University / Karmanos Cancer Institute
Siteman Cancer Center at Washington University
Dartmouth Hitchcock Medical Center
University of New Mexico Cancer Center
Presbyterian Rust Medical Center / Jorgensen Cancer Center
Montefiore Medical Center-Weiler Hospital
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Case Comprehensive Cancer Center
Ohio State University Comprehensive Cancer Center
Fox Chase Cancer Center
Contact: systems coordinator
Thomas Jefferson University Hospital
Abington Memorial Hospital-Asplundh Cancer Pavilion
University of Virginia Cancer Center
Fred Hutch / University of Washington Cancer Consortium
Trial Phase Phase III
Trial Type Treatment
- Primary ID 213361
- Secondary IDs NCI-2019-04891, ENGOT-EN6, GOG-3031, 4010-03-001
- Clinicaltrials.gov ID NCT03981796