Brief Title
A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
Official Title
A Phase 3, Randomized, Double-blind, Multicenter Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY)
Brief Summary
This is a 2 part study. Part 1 is to evaluate the efficacy and safety of dostarlimab plus
carboplatin-paclitaxel followed by dostarlimab versus placebo plus carboplatin-paclitaxel
followed by placebo; and Part 2 is to evaluate the efficacy and safety of dostarlimab plus
carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus
carboplatin-paclitaxel followed by placebo in participants with recurrent or primary advanced
(Stage III or IV) endometrial cancer. Part 1 has completed enrollment, and Part 2 is open for
enrollment. Both Parts consist of a Screening Period, Treatment Period, an End of Treatment
(EOT) Visit, a Safety Follow-up Visit, and a Survival Assessment Period. In Part 2,
participants will be randomized 1:2 to receive either carboplatin/paclitaxel/placebo or
Dostarlimab/carboplatin/paclitaxel followed by Dostarlimab/niraparib or placebo iv/oral
maintenance.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Part 1 and 2: Progression-Free Survival (PFS) - based on blinded independent central review (BICR)
Secondary Outcome
Part 1 and 2: Overall survival (OS)
Condition
Neoplasms
Intervention
Dostarlimab
Study Arms / Comparison Groups
Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
740
Start Date
July 18, 2019
Completion Date
March 31, 2026
Primary Completion Date
July 30, 2021
Eligibility Criteria
Inclusion Criteria:
Part 1 and Part 2:
- Female participant is at least 18 years of age
- Participant has histologically or cytologically proven endometrial cancer with
recurrent or advanced disease.
- 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 post-operative 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 percent 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 regardless of
the presence of evaluable or measurable disease; d) Participant has first recurrent
disease and is naïve to systemic anticancer therapy; e) Participant has received prior
neo-adjuvant/adjuvant systemic anticancer therapy 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.
- Part 2 only:
- Participants must have normal blood pressure (BP) or adequately treated and controlled
hypertension (systolic BP <=140 millimeter of mercury (mmHg) and diastolic BP <=90
mmHg).
- Participants must be able to take medication orally, by mouth (PO).
Exclusion Criteria:
- Part 1 and Part 2:
- Participant has received neo-adjuvant/adjuvant systemic anticancer therapy for primary
Stage III or IV disease and: a) has not had a recurrence or PD prior to first dose on
the study OR b) has had a recurrence or PD within 6 months of completing systemic
anticancer therapy treatment prior to first dose on the study.
- Participant has had >1 recurrence of endometrial cancer.
- Participant has received prior therapy with an anti-programmed cell death protein 1
(anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), or anti-PD-ligand 2 (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 not recovered (i.e., to Grade <=1 or to Baseline) from cytotoxic
therapy induced AEs or has received transfusion of blood products (including platelets
or red blood cells) or administration of colony-stimulating factors (including
granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage
colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 21 days
prior to the first dose of study drug.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical
disorder, nonmalignant systemic disease, or active infection requiring systemic
therapy.
- Participant has received, or is scheduled to receive, a live vaccine within 30 days
before first dose of study treatment, during study treatment, and for up to 180 days
after receiving the last dose of study treatment.
- Part 2 only:
- Participant has clinically significant cardiovascular disease
- Participant has any known history or current diagnosis of myelodysplastic syndrome
(MDS) or acute myeloid leukemia (AML).
- Participant is at increased bleeding risk due to concurrent conditions.
- Participant has participated in Part 1 of this study.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
GSK Clinical Trials, 877-379-3718, [email protected]
Location Countries
Belarus
Location Countries
Belarus
Administrative Informations
NCT ID
NCT03981796
Organization ID
213361
Secondary IDs
ENGOT-EN6
Responsible Party
Sponsor
Study Sponsor
Tesaro, Inc.
Collaborators
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Study Sponsor
GSK Clinical Trials, Study Director, GlaxoSmithKline
Verification Date
July 2021