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
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Progression-Free Survival (PFS) - Investigator assessment
Secondary Outcome
Progression free survival (PFS) - Blinded Independent Central Review (BICR)
Condition
Neoplasms
Intervention
Dostarlimab
Study Arms / Comparison Groups
Dostarlimab plus Carboplatin-paclitaxel
Description: Participants will be administered dostarlimab 500 milligram (mg) every 3 weeks (Q3W) as 30-minute infusion intravenously (IV) from Cycle 1 (each cycle is 21 days) to Cycle 6 and dostarlimab 1000 mg every 6 weeks (Q6W) (Cycle 7 until progression of disease, toxicity, withdrawal of consent, Investigator's decision, or death, whichever occurs first); followed by Carboplatin 5 mg/milliliter (mL)/minute (min) and paclitaxel 175 mg per square meter (mg/m^2) Q3W as 30-minute infusion IV from Cycle 1 to Cycle 6.
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
470
Start Date
July 18, 2019
Completion Date
May 31, 2027
Primary Completion Date
October 11, 2021
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
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
August 2020