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Trial record 1 of 1 for:    4010-03-001 / ENGOT EN-6 / GOG-3031 | Endometrial Cancer
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A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer (RUBY)

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ClinicalTrials.gov Identifier: NCT03981796
Recruitment Status : Recruiting
First Posted : June 11, 2019
Last Update Posted : April 20, 2021
Sponsor:
Collaborators:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
Information provided by (Responsible Party):
Tesaro, Inc.

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.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: Dostarlimab Drug: Placebo Drug: Carboplatin Drug: Paclitaxel Drug: Niraparib Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 740 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The participant, Investigator, study staff, and the Sponsor study team and its representatives will be blinded to the assigned treatment.
Primary Purpose: Treatment
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)
Actual Study Start Date : July 18, 2019
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : February 16, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab Biological: Dostarlimab
Participants will be administered dostarlimab
Other Name: TSR-042

Drug: Carboplatin
Participants will be administered carboplatin

Drug: Paclitaxel
Participants will be administered paclitaxel

Placebo Comparator: Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placebo Drug: Placebo
Participants will be administered placebo

Drug: Carboplatin
Participants will be administered carboplatin

Drug: Paclitaxel
Participants will be administered paclitaxel

Active Comparator: Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparib Biological: Dostarlimab
Participants will be administered dostarlimab
Other Name: TSR-042

Drug: Carboplatin
Participants will be administered carboplatin

Drug: Paclitaxel
Participants will be administered paclitaxel

Drug: Niraparib
Participants will be administered niraparib

Placebo Comparator: Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placebo Drug: Placebo
Participants will be administered placebo

Drug: Carboplatin
Participants will be administered carboplatin

Drug: Paclitaxel
Participants will be administered paclitaxel




Primary Outcome Measures :
  1. Part 1 and 2: Progression-Free Survival (PFS) - based on blinded independent central review (BICR) [ Time Frame: Up to 6 years and 9 months ]
    PFS is based on BICR and is defined as the time from the date of randomization to the earliest date of radiographic assessment of progression of disease (PD) or death by any cause in the absence of (PD), whichever occurs first as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.


Secondary Outcome Measures :
  1. Part 1 and 2: Overall survival (OS) [ Time Frame: Up to 6 years and 9 months ]
    OS is defined as the time from randomization to the date of death by any cause.

  2. Part 1 and 2: Progression free survival (PFS) - Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
    PFS based on Investigator Assessment is defined as the time from the date of randomization to the earliest date of assessment of PD or death by any cause in the absence of PD whichever occurs first per RECIST v.1.1.

  3. Part 1 and 2: Objective response rate (ORR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
    ORR based on BICR and Investigator assessment is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).

  4. Part 1 and 2: Duration of response (DOR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
    DOR based on BICR and Investigator assessment is defined as the time from first documentation of CR or PR until the time of first documentation of subsequent PD per RECIST v.1.1 or death by any cause in the absence of PD per RECIST v.1.1, whichever occurs first.

  5. Part 1 and 2: Disease control rate (DCR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
    DCR based on BICR and Investigator assessment is defined as the proportion of participants who have achieved a BOR of CR, PR, or stable disease (SD) per RECIST v.1.1.

  6. Part 1 and 2: Patient-reported outcomes (PROs) in the European Quality of Life scale, 5-Dimensions, 5-Levels (EQ-5D-5L) [ Time Frame: Up to 6 years and 9 months ]
    EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases.

  7. Part 1 and 2: PROs in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30 [Core]) [ Time Frame: Up to 6 years and 9 months ]
    EORTC QLQ-C30 is validated questionnaire to assess overall health-related quality of life in participants with cancer.

  8. Part 1 and 2: PROs in the EORTC Quality of Life Questionnaire (QLQ-EN24 [Endometrial Cancer Module]) [ Time Frame: Up to 6 years and 9 months ]
    EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in participants with all stages of endometrial cancer.

  9. Part 1 and 2: Progression-free survival 2 (PFS2) [ Time Frame: Up to 6 years and 9 months ]
    PFS2 is defined as the time from treatment randomization to the date of assessment of progression on the first subsequent anticancer therapy following study treatment or death by any cause, whichever is earlier.

  10. Part 1 and 2: Number of participants with adverse events (AEs), Serious adverse events (SAEs), adverse event of special interests (AESIs), suspected unexpected serious adverse reaction (SUSAR) and treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 6 years and 9 months ]
  11. Part 1 and 2: Number of participants with clinically significant changes in clinical laboratory parameters, vital signs, physical examination, electrocardiogram (ECG) and participants reporting the intake of concomitant medication [ Time Frame: Up to 6 years and 9 months ]
  12. Part 1 and 2: Number of participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Scores [ Time Frame: Up to 6 years and 9 months ]
    Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.

  13. Part 1 and 2: Minimum observed concentration (Cmin) and maximum observed concentration (Cmax) of dostarlimab (micrograms per milliliter) [ Time Frame: Predose (Day 1) and postdose (Day 1) of Cycles 1, 2, 6, 7, 10, 15, and 20 (Cycle 1, 2, 6 is 21 days and Cycle 7, 10, 15, 20 is 42 days) ]
    Blood samples to be collected predose (within 1 hour prior to infusion) and postdose (within 1 hour after the end of infusion) on Day 1 of Cycles 1, 2, 6, 7, 10, 15, and 20.

  14. Part 1 and 2: Cmin and Cmax at steady state of dostarlimab (micrograms per milliliter) [ Time Frame: Predose (Day 1) and postdose (Day 1) of Cycles 1, 2, 6, 7, 10, 15, and 20 (Cycle 1, 2, 6 is 21 days and Cycle 7, 10, 15, 20 is 42 days) ]
    Blood samples to be collected predose (within 1 hour prior to infusion) and postdose (within 1 hour after the end of infusion) on Day 1 of Cycles 1, 2, 6, 7, 10, 15, and 20.

  15. Part 2: Cmin and Cmax of niraparib (micrograms per milliliter) [ Time Frame: Predose (Day 1) and 3 hours postdose (Day 1) of Cycles 7 and 8 and Predose (Day 1) of Cycles 10 and 14 (each cycle is 42 days) ]
    Blood samples for niraparib PK to be collected predose (within 30 minutes before scheduled dose) and 3 hours postdose (+/-30 minutes) on Day 1 of Cycle 7 and Cycle 8. Additional blood samples for PK on Day 1 of Cycle 10 and Cycle 14 will be collected at predose (within 30 minutes before scheduled dose).

  16. Part 2: Cmin and Cmax at steady state of niraparib (micrograms per milliliter) [ Time Frame: Predose (Day 1) and 3 hours postdose (Day 1) of Cycles 7 and 8 and Predose (Day 1) of Cycles 10 and 14 (each cycle is 42 days) ]
    Blood samples for niraparib PK to be collected predose (within 30 minutes before scheduled dose) and 3 hours postdose (+/-30 minutes) on Day 1 of Cycle 7 and Cycle 8. Additional blood samples for PK on Day 1 of Cycle 10 and Cycle 14 will be collected at predose (within 30 minutes before scheduled dose).

  17. Part 1 and 2: Number of participants with anti-drug antibodies (ADA) against dostarlimab [ Time Frame: Predose (Day 1) ]
    All the predose samples collected for Dostarlimab PK analysis to be evaluated for the presence of ADAs and neutralizing antibody in a tiered approach using electrochemiluminescence.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03981796


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Show Show 149 study locations
Sponsors and Collaborators
Tesaro, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03981796    
Other Study ID Numbers: 213361
ENGOT-EN6 ( Other Identifier: ENGOT )
GOG-3031 ( Other Identifier: GOG )
4010-03-001 ( Other Identifier: Tesaro )
First Posted: June 11, 2019    Key Record Dates
Last Update Posted: April 20, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tesaro, Inc.:
Dostarlimab
Carboplatin
Paclitaxel
Niraparib
Recurrent or primary advanced endometrial cancer
TSR-042
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Paclitaxel
Carboplatin
Niraparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors