Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Carboplatin

Niraparib

Dostarlimab

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) 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.

Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo.

Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab.

Participants will receive oral capsules of niraparib as a unit dosage strength of 100 milligrams (mg).

Participants will receive 30 minutes intravenous (IV) infusions of 1000 mg dostarlimab on Day 1 every 6 weeks.

Dostarlimab (TSR-042)

Participants will receive SOC that includes paclitaxel 175 milligrams per square meter (mg/m\^2) on day 1 every 21 days + carboplatin area under the curve (AUC) of 5 to 6 milligrams per milliliter per minute (mg/mL/min) on day 1 every 21 days +/- bevacizumab 7.5 milligrams per kilograms (mg/kg) every 21 days or 15 mg/kg every 21 days for a total of 15 months.

Standard of care

Participants will receive 1000 mg of dostarlimab-placebo on day 1 every 6 weeks to continue up to 3 years in the absence of disease progression, unacceptable toxicity, participant withdrawal, or investigator decision

Dostarlimab-Placebo

Participants will receive oral capsules of niraparib-placebo as a unit dosage strength of 100 mg.

Niraparib-Placebo

GSK Clinical Trials

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 the progression-free survival (PFS) for participants receiving dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus participants receiving SOC with chemotherapy followed by niraparib maintenance. This comparison will be investigated both in the PD-L1 positive and overall population of newly diagnosed stage III or IV advanced non-mucinous epithelial ovarian cancer participants and also to compare PFS of all participants with Stage III or IV high-grade non-mucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab (TSR-042), 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.

Female participants will be included in the study.

A 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

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

To compare the PFS of PD-L1 positive participants with Stage III or IV non-mucinous epithelial ovarian cancer given first-line treatment with the combination of dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus SOC chemotherapy +/- bevacizumab followed by niraparib maintenance +/- bevacizumab. 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. PFS will be evaluated by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria.

To compare the PFS of all participants with Stage III or IV high-grade nonmucinous epithelial ovarian cancer given first-line treatment with the combination of dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus SOC chemotherapy +/- bevacizumab followed by niraparib maintenance +/- bevacizumab. 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. PFS will be evaluated by investigator assessment per RECIST v.1.1 criteria.

BICR determined PFS will be assessed as per RECIST criteria.

OS is defined as the date of randomization to the date of death by any cause.

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.

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.

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.

Following events are categorized as irAEs: 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.

Following events are categorized as irAEs: 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.

Performance status will be assessed using the ECOG performance status scale: ranging from Grade 0 to 5, Grade 0 denoting fully active and Grade 5 denoting death.

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.

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.

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.

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.

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/dimensions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is measured by 5-point Likert scale (no problems, slight problems, moderate problems, severe problems and extreme problems).

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). Response options are 1 to 4. Higher score indicates better health-related quality of life.

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). Response options are 1 to 4. Higher score indicates better health-related quality of life.

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/ gastrointestinal (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. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in all the 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. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

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). Response options are 1 to 4. Higher score indicates better health-related quality of life.

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. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

TFST is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy or death, whichever occurs first.

TSST is defined as the time from randomization until the start date of the second subsequent anti-cancer therapy or death, whichever occurs first.

PFS2 is defined as the time from randomization until PD per investigator's assessment after starting follow-up anti-cancer therapy or death due to any cause, whichever occurs first.

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.

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.

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.

DCR, defined as the proportion of participants with a best overall response of CR, PR, or stable disease (SD), as assessed by RECIST v.1.1 criteria.

DCR, defined as the proportion of participants with a best overall response of CR, PR, or SD, as assessed by RECIST v.1.1 criteria.

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.

Blood samples will be collected for pharmacokinetic analysis of dostarlimab.

Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.

Blood samples will be collected for pharmacokinetic analysis of niraparib.

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Tesaro, Inc.

The starting dose is 300mg or 200mg QD based on the subject's baseline body weight or baseline platelet count

Hong Zheng, M.D.

This study is a multicenter, open-label, single-arm phase II clinical trial investigating the efficacy and safety of niraparib monotherapy maintenance in HRD-positive newly diagnosed advanced epithelial ovarian cancer (EOC), including primary peritoneal and/or fallopian tube tumors, following response to front-line chemotherapy in combination with bevacizumab. A total of 116 patients will be enrolled.

Niraparib Maintenance in HRD-Positive Advanced Ovarian Cancer Following Front-Line Chemotherapy + Bevacizumab

Chemotherapy Combined With Bevacizumab Followed by Niraparib Monotherapy in Newly Diagnostic Advanced Ovarian Cancer With HRD Positive : A Perspective, Multicenter, Single-arm Phase II Trial

PFS rate at 24 months is defined as the percentage of participants who have not progressed or died within 24 months after niraparib treatment initiation. Progression was assessed by response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria per Investigator assessment. Survival rate is the percentage of participants without progression assessed by RECIST v1.1 or death by the landmark timepoint. Confidence intervals was constructed using exact method.

PFS rate at 12 months after niraparib treatment initiation according to investigator assessment

Time from the date of initiation of maintenance therapy with niraparib to the date of the first subsequent anticancer therapy or death, whichever occurred first.

Time from the date of initiation of maintenance therapy with niraparib to the date of the second subsequent anticancer therapy or death, whichever occurred first.

Time from the date of initiation of maintenance therapy with niraparib to the date of disease progression in our study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A 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	Ovarian Neoplas... Ovarian, Fallop...	Niraparib Dostarlimab (TS... Standard of car... Dostarlimab-Pla... Niraparib-Place...	18 Years -	Tesaro, Inc.
Niraparib Maintenance in HRD-Positive Advanced Ovarian Cancer Following Front-Line Chemotherapy + Bevacizumab	NCT06141265	Ovarian, Fallop...	Niraparib	18 Years - 75 Years	Peking University Cancer Hospital & Institute

Spots Global Cancer Trial Database for ovarian, fallopian tube and primary peritoneal carcinoma