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A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

NCT03602859

Description:

Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic changes. The high expression of vascular endothelial growth factor (VEGF) receptor, programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA) damage in ovarian tumors provide several targets for treatment and maintenance of disease response. Given the unmet medical need of participants with advanced or metastatic ovarian cancer, this study design will enable investigators to provide participants with current SOC for ovarian cancer for the duration of the study. This is a global, multicenter, randomized, double-blind, controlled Phase 3 study that will primarily compare progressive survival rate of PD-L1 positive patients and also to compare progression-free survival (PFS) of all participants with Stage III or IV high-grade nonmucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab, and niraparib to SOC platinum-based combination therapy. The currently recommended SOC therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab. Participants will receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2). Concurrent bevacizumab use must be determined prior to randomization at cycle 2. Approximately 1228 participants will be enrolled into the study and the duration of the study will be approximately 78 months.

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT03602859

Trial Eligibility

Document

Title

  • Brief Title: A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
  • Official Title: ENGOT-0V44 The FIRST (First-line Ovarian Cancer Treatment With Niraparib Plus TSR-042) Study: A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 213350
  • SECONDARY ID: 3000-03-005
  • NCT ID: NCT03602859

Conditions

  • Ovarian Neoplasms
  • Ovarian Cancer

Interventions

DrugSynonymsArms
NiraparibZEJULAParticipants receiving SOC+dostarlimab
Dostarlimab (TSR-042)Participants receiving SOC+dostarlimab
PlaceboParticipants receiving SOC+niraparib
Standard of careParticipants receiving SOC+dostarlimab
Dostarlimab/PlaceboParticipants receiving SOC+niraparib
Niraparib/PlaceboParticipants receiving SOC+placebo

Purpose

Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic changes. The high expression of vascular endothelial growth factor (VEGF) receptor, programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA) damage in ovarian tumors provide several targets for treatment and maintenance of disease response. Given the unmet medical need of participants with advanced or metastatic ovarian cancer, this study design will enable investigators to provide participants with current SOC for ovarian cancer for the duration of the study. This is a global, multicenter, randomized, double-blind, controlled Phase 3 study that will primarily compare progressive survival rate of PD-L1 positive patients and also to compare progression-free survival (PFS) of all participants with Stage III or IV high-grade nonmucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab, and niraparib to SOC platinum-based combination therapy. The currently recommended SOC therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab. Participants will receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2). Concurrent bevacizumab use must be determined prior to randomization at cycle 2. Approximately 1228 participants will be enrolled into the study and the duration of the study will be approximately 78 months.

Trial Arms

NameTypeDescriptionInterventions
Participants receiving SOC+placeboPlacebo ComparatorParticipants in this arm will receive SOC (carboplatin+paclitaxel+bevacizumab) in cycle 1 followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of bevacizumab along with niraparib placebo and dostarlimab placebo.
  • Placebo
  • Standard of care
  • Dostarlimab/Placebo
  • Niraparib/Placebo
Participants receiving SOC+niraparibActive ComparatorParticipants in this arm will receive SOC in cycle 1 followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of bevacizumab with niraparib and dostarlimab placebo.
  • Niraparib
  • Placebo
  • Standard of care
  • Dostarlimab/Placebo
Participants receiving SOC+dostarlimabExperimentalParticipants in this arm will receive SOC in cycle 1 followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of bevacizumab with niraparib and dostarlimab.
  • Niraparib
  • Dostarlimab (TSR-042)
  • Standard of care

Eligibility Criteria

        Inclusion criteria:

          -  Participants must be female, >=18 years of age, able to understand the study
             procedures, and agree to participate in the study by providing written informed
             consent.

          -  Participants with a histologically confirmed diagnosis of high-grade nonmucinous
             epithelial ovarian (serous, endometrioid, clear cell, carcinosarcoma, an mixed
             pathologies), fallopian tube, or primary peritoneal cancer that is Stage III or IV
             according to the International Federation of Gynecology and Obstetrics (FIGO) or
             tumor, node and metastasis staging criteria.

          -  All participants with Stage IV disease are eligible. This includes those with
             inoperable disease, those who undergo primary debulking surgery (PDS); (complete
             cytoreduction [CC0] or macroscopic disease), or those for whom neoadjuvant
             chemotherapy (NACT) is planned.

          -  Participants with Stage III are eligible if they meet one or more of the following
             criteria:

               1. Stage IIIC participants with CC0 resection if they meet the following criteria:
                  Aggregate >=5 cm extra-pelvic disease during PDS as assessed by the investigator

               2. All participants with inoperable Stage III disease.

               3. All Stage III participants with macroscopic residual tumor (per investigator
                  judgement) following PDS.

               4. All Stage III participants for whom NACT is planned..

          -  Participants must provide a blood sample for circulating tumor deoxyribonucleic acid
             (ctDNA) homologous recombinant repair (HRR) testing at pre-screening or screening.

          -  Participant must provide a minimum of formalin-fixed paraffin embedded (FFPE) block at
             pre-screening or screening for PD-L1, homologous recombinant deficiency (HRD) testing.

          -  Participants of childbearing potential must have a negative serum or urine pregnancy
             test (beta human chorionic gonadotropin) within 3 days prior to receiving the first
             dose of study treatment.

          -  Participants must be postmenopausal, free from menses for >1 year, surgically
             sterilized, or willing to use highly effective contraception to prevent pregnancy or
             must agree to abstain from activities that could result in pregnancy throughout the
             study, starting with enrollment through 180 days after the last dose of study
             treatment.

          -  Participants must have adequate organ function: Absolute neutrophil count ANC
             >=1500/micro liter (μL;) Platelet count >=100000/μL; Hemoglobin >=9 grams per
             deciliter (g/dL); Serum creatinine <=1.5 × upper limit of normal (ULN) or calculated
             creatinine clearance >=60 milliliters per minute (mL/min) using the Cockcroft-Gault
             equation; total bilirubin <=1.5 × ULN or direct bilirubin <=1.5 × ULN; AST and ALT
             <=2.5 × ULN unless liver metastases are present, in which case they must be <=5 × ULN.

          -  Participants must have an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

          -  Participants must have normal blood pressure (BP) or adequately treated and controlled
             hypertension (systolic BP <=140 millimeters of mercury (mmHg) and/or diastolic BP <=90
             mmHg).

          -  Participants must agree to complete health related quality of life (HRQoL)
             questionnaires throughout the study.

          -  Participants must be able to take oral medication.

        Exclusion Criteria:

          -  Participant has mucinous, germ cell, transitional cell, or undifferentiated tumor.

          -  Participant has low-grade or Grade 1 epithelial ovarian cancer.

          -  Stage III participant with R0 resection after PDS (i.e., no macroscopic residual
             disease, unless the participant has aggregate 5cm extra-pelvic disease during primary
             debulking surgery.

          -  Participant has not adequately recovered from prior major surgery.

          -  Participant has a known condition, therapy, or laboratory abnormality that might
             confound the study results or interfere with the participant's participation for the
             full duration of the study treatment in the opinion of the investigator.

          -  Participant is pregnant or is expecting to conceive children while receiving study
             drug or for up to 180 days after the last dose of study drug. Participant is
             breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose
             of study drug (women should not breastfeed or store breastmilk for use, during
             niraparib treatment and for 30 days after receiving the final dose of study
             treatment).

          -  Participant has known active central nervous system metastases, carcinomatous
             meningitis, or both.

          -  Participant has clinically significant cardiovascular disease (example, significant
             cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction,
             uncontrolled cardiac arrhythmia or unstable angina <6 months to enrollment, New York
             Heart Association Grade 2 or greater congestive heart failure, serious cardiac
             arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and
             history of cerebrovascular accident within 6 months).

          -  Participant has a bowel obstruction by clinical symptoms or computed tomography (CT)
             scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula,
             gastrointestinal perforation, or intra-abdominal abscess.

          -  Participant initiating bevacizumab as SOC has proteinuria as demonstrated by urine
             protein:creatinine ratio >=1.0 at Screening or urine dipstick for proteinuria >=2
             (participants discovered to have >=2 proteinuria on dipstick at baseline should
             undergo a 24-hour urine collection and must demonstrate <2 grams (g) of protein in 24
             hours to be eligible).

          -  Participant has any known history or current diagnosis of myelodysplastic syndrome
             (MDS) or acute myeloid leukemia (AML).

          -  Participant has been diagnosed and/or treated with any therapy for invasive cancer <5
             years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy
             (example, trastuzumab) less than 3 years from enrollment, or completed adjuvant
             hormonal therapy less than 4 weeks from enrollment. - Participants with definitively
             treated non-invasive malignancies such as cervical carcinoma in situ, ductal carcinoma
             in situ, Grade 1 or 2, Stage IA endometrial cancer, or non-melanomatous skin cancer
             are allowed.

          -  Participant is at increased bleeding risk due to concurrent conditions (example, major
             injuries or major surgery within the past 28 days prior to start of study treatment
             and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid
             hemorrhage, or clinically significant hemorrhage within the past 3 months).

          -  Participant is immunocompromised. Participants with splenectomy are allowed.
             Participants with well-controlled known HIV are allowed if they meet all of the
             following criteria: Cluster of differentiation 4 >=350/μL and viral load <400
             copies/mL; No history of acquired immunodeficiency syndrome-defining opportunistic
             infections within 12 months prior to enrolment; No history of HIV-associated
             malignancy for the past 5 years; Concurrent anti-retroviral therapy as per the most
             current National Institutes of Health (NIH) Guidelines for the Use of Anti-retroviral
             Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study
             enrolment.

          -  Participant has known active hepatitis B (example, hepatitis B surface antigen
             reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid [qualitative] is
             detected).

          -  Participant is considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease, or active, uncontrolled infection. Specific
             examples include, but are not limited to, history of non-infectious pneumonitis that
             required steroids, current pneumonitis, uncontrolled autoimmune disease, uncontrolled
             ventricular arrhythmia, recent myocardial infarction within 90 days of consent,
             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 has had investigational therapy administered within 4 weeks or within a
             time interval less than at least 5 half-lives of the investigational agent, whichever
             is longer, prior to the first scheduled day of dosing in this study.

          -  Participant has received a live vaccine within 14 days of planned start of study
             therapy. Seasonal influenza vaccines that do not contain live viruses are allowed.

          -  Participant has a known contraindication or uncontrolled hypersensitivity to the
             components of paclitaxel, carboplatin, niraparib, bevacizumab, dostarlimab, or their
             excipients.

          -  Prior treatment for high-grade nonmucinous epithelial ovarian, fallopian tube, or
             peritoneal cancer (immunotherapy, anti-cancer therapy, radiation therapy).

          -  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
             (example, 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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS for PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:To compare the PFS of PD-L1 positive participants with Stage III or IV non-mucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab, and niraparib to standard of care platinum-based combination therapy as first-line treatment. PFS is defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression. Progression free survival will be evaluated by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria.

Secondary Outcome Measures

Measure:Blinded Independent Central Review (BICR) for PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:BICR determined by PFS will be derived as per RECIST v1.
Measure:BICR for all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:BICR determined by PFS will be derived as per RECIST v1.1
Measure:PFS per investigator-assessed immune-related of PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:PFS will be assessed as per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria.
Measure:PFS per investigator-assessed immune-related for all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:PFS will be assessed as per irRECIST criteria.
Measure:Overall Survival (OS) of PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:The OS is defined as the date of randomization to the date of death by any cause.
Measure:OS of all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:The OS is defined as the date of randomization to the date of death by any cause.
Measure:Number of PD-L1 positive participants with treatment-emergent adverse events (TEAEs)
Time Frame:Up to 5 years
Safety Issue:
Description:TEAEs are defined as, any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Measure:Number of overall participants with TEAEs
Time Frame:Up to 5 years
Safety Issue:
Description:TEAEs are defined as, any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Measure:Number of PD-L1 positive participants with serious adverse events (SAEs)
Time Frame:Up to 5 years
Safety Issue:
Description:SAEs are any adverse event that may result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital abnormality or birth defect, is an important medical event.
Measure:Number of overall participants with SAEs
Time Frame:Up to 5 years
Safety Issue:
Description:SAEs are any adverse event that may result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital abnormality or birth defect, is an important medical event.
Measure:Number of PD-L1 positive participants with treatment discontinuations or dose delays or dose reductions due to adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Adverse events are any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.
Measure:Number of all the participants with treatment discontinuations or dose delays or dose reductions due to adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Adverse events are any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.
Measure:Number of PD-L1 positive participants with immune-related adverse events of interest (irAEIs)
Time Frame:Up to 5 years
Safety Issue:
Description:Following events are categorized as irAEIs: Diarrhea/colitis, aspartate aminotransferase (AST) or alanine aminotransferase (ALT; >3 and <=5 X upper limit of normal [ULN]), or increased bilirubin, type 1 diabetes mellitus (T1DM) or hyperglycemia, immune-related encephalitis, uveitis, myositis, hypophysitis, adrenal insufficiency, hypo- and hyperthyroidism, infusion-related reaction, pneumonitis, immune-related rash, renal failure or nephritis and recurrence of adverse events after resolution to Grade <=1.
Measure:Number of all the participants with irAEIs
Time Frame:Up to 5 years
Safety Issue:
Description:Following events are categorized as irAEIs: Diarrhea/colitis, AST or ALT (>3 and <=5 X ULN), or increased bilirubin, T1DM or hyperglycemia, immune-related encephalitis, uveitis, myositis, hypophysitis, adrenal insufficiency, hypo- and hyperthyroidism, infusion-related reaction, pneumonitis, immune-related rash, renal failure or nephritis and recurrence of AEs after resolution to Grade <=1.
Measure:Number of PD-L1 positive participants with changes in Eastern Cooperative Oncology Group (ECOG) performance status
Time Frame:Up to 5 years
Safety Issue:
Description:Performance status will be assessed using the ECOG scale
Measure:Number of overall participants with changes in ECOG performance status
Time Frame:Up to 5 years
Safety Issue:
Description:Performance status will be assessed using the ECOG scale
Measure:Number of PD-L1 positive participants with abnormal hematology results
Time Frame:Up to 5 years
Safety Issue:
Description:Blood samples will be collected for the analysis of hematologic parameters including: hemoglobin, platelet count, white blood cell count, differential white blood cell count, coagulation factors-International normalized ratio (INR) and activated partial thromboplastin time.
Measure:Number of all the participants with abnormal hematology results
Time Frame:Up to 5 years
Safety Issue:
Description:Blood samples will be collected for the analysis of hematologic parameters including: hemoglobin, platelet count, white blood cell count, differential white blood cell count, coagulation factors-INR and activated partial thromboplastin time.
Measure:Number of PD-L1 positive participants with abnormal blood chemistry results
Time Frame:Up to 5 years
Safety Issue:
Description:Blood samples will be collected for the analysis of clinical chemistry parameters including: amylase, thyroid function (thyroid stimulating hormone [TSH]), urea or blood urea nitrogen, creatinine, albumin, total protein, ALT, AST, total bilirubin, Glucose, Magnesium, Calcium, Chloride, Potassium and Sodium.
Measure:Number of all the participants with abnormal blood chemistry results
Time Frame:Up to 5 years
Safety Issue:
Description:Blood samples will be collected for the analysis of clinical chemistry parameters including:: amylase, thyroid function (TSH), urea or blood urea nitrogen, creatinine, albumin, total protein, ALT, AST, total bilirubin, Glucose, Magnesium, Calcium, Chloride, Potassium and Sodium.
Measure:Change from Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) assessment among PD-L1 positive participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Measure:Change from Baseline in the EQ-5D-5L assessment among all participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Measure:Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) assessment among PD-L1 positive participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/quality of life scale (GHS/QOL), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea and financial difficulties).
Measure:Change from Baseline in the EORTC-QLQ-C30 assessment among all the participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).
Measure:Change from Baseline in the EORTC-QLQ Ovarian Cancer Module OV28 (EORTC-QLQ-OV28) assessment among PD-L1 positive participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste.
Measure:Change from Baseline in the EORTC-QLQ-OV28 assessment among all the participants
Time Frame:Baseline and Up to 5 years
Safety Issue:
Description:EORTC QLQ-OV28 is a validated questionnaire to assess the overall he PFS2, health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste.
Measure:Time to symptom worsening in the EQ-5D-5L assessment among the PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Measure:Time to symptom worsening in the EQ-5D-5L assessment among all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Measure:Time to symptom worsening in the EORTC-QLQ-C30 assessment among the PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).
Measure:Time to symptom worsening in the EORTC QLQ-C30 assessment among all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).
Measure:Time to symptom worsening in the EORTC-QLQ-OV28 assessment among the PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-OV28 is a validated questionnaire to assess the overall he PFS2, health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste.
Measure:Time to symptom worsening in the EORTC-QLQ-OV28 assessment among all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-OV28 is a validated questionnaire to assess the overall he PFS2, alth-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste.
Measure:Time to first subsequent therapy (TFST) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:TFST is defined as the duration between the date of randomization in the current study to the start date of the first subsequent anticancer therapy.
Measure:TFST in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:TFST is defined as the duration between the date of randomization in the current study to the start date of the first subsequent anticancer therapy.
Measure:Time to second subsequent therapy (TSST) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:TSST, defined as the duration between the date of randomization in the current study to the start date of the second subsequent anticancer therapy.
Measure:TSST in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:TSST, defined as the duration between the date of randomization in the current study to the start date of the second subsequent anticancer therapy.
Measure:Time to progression on next-line therapy (PFS2,) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:PFS2, defined as the time from randomization to the earlier date of assessment of progression on the next anticancer therapy following study treatment or death by any cause as assessed by the investigator.
Measure:PFS2 in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:PFS2, defined as the time from randomization to the earlier date of assessment of progression on the next anticancer therapy following study treatment or death by any cause as assessed by the investigator.
Measure:Objective Response Rate (ORR) among PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) on study treatment as assessed by RECIST v.1.1 criteria for participants with measurable disease. ORR will also be assessed per irRECIST criteria.
Measure:ORR among all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) on study treatment as assessed by RECIST v.1.1 criteria for participants with measurable disease. ORR will also be assessed per irRECIST criteria.
Measure:Pathologic complete response (pCR) rate among PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:pCR rate, per investigator assessment, defined as the rate of pathologic complete responseas assessed by the evaluation of residual microscopic disease at the time of surgery in neoadjuvant participants.
Measure:pCR rate among all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:pCR rate, per investigator assessment, defined as the rate of pathologic complete responseas assessed by the evaluation of residual microscopic disease at the time of surgery in neoadjuvant participants.
Measure:Duration of response (DOR) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:DOR, defined as the time from first documentation of CR or PR until the time of first documentation of PD as assessed by RECIST v.1.1, or death by any cause in the absence of progression, whichever occurs first. DOR will also be assessed per irRECIST criteria.
Measure:DOR in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:DOR, defined as the time from first documentation of CR or PR until the time of first documentation of PD as assessed by RECIST v.1.1, or death by any cause in the absence of progression, whichever occurs first. DOR will also be assessed per irRECIST criteria.
Measure:Disease control rate (DCR) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:DCR, defined as the proportion of participants with a best overall response of CR, PR, or stable disease, as assessed by RECIST v.1.1 criteria. DCR will also be assessed per irRECIST criteria.
Measure:DCR in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:DCR, defined as the proportion of participants with a best overall response of CR, PR, or stable disease, as assessed by RECIST v.1.1 criteria. DCR will also be assessed per irRECIST criteria.
Measure:Maintenance progression-free survival (MPFS) in PD-L1 positive participants
Time Frame:Up to 5 years
Safety Issue:
Description:MPFS, defined as the time from the date of the first maintenance period dose to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the investigator. Progression will be assessed by RECIST v.1.1 criteria. MPFS will also be assessed per irRECIST criteria.
Measure:MPFS in all the participants
Time Frame:Up to 5 years
Safety Issue:
Description:MPFS, defined as the time from the date of the first maintenance period dose to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the investigator. Progression will be assessed by RECIST v.1.1 criteria. MPFS will also be assessed per irRECIST criteria.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • FIRST
  • FIRST trial
  • Niraparib
  • Dostarlimab (TSR-042)

Last Updated

June 2, 2021