Trial Comparing Niraparib-bevacizumab-Dostarlimab and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer

NCT03806049 | Withdrawn Phase 3 DMC

• 1 other identifier: ENGOT-OV42 / NSGO-AVATAR
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 8

Brief Summary

ENGOT-OV42 / NSGO-AVATAR: This three-arm randomized trial is to demonstrate efficacy of niraparib-bevacizumab-dostarlimab triplet combination against standard of care treatment and to demonstrate efficacy of niraparib-bevacizumab-dostarlimab triplet combination against niraparib-bevacizumab doublet combination for patients with platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer

Conditions

Ovarian Cancer

Keywords

chemotherapy-free regimen; niraparib; bevacizumab; dostarlimab; recurrent ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.

  42 months

Secondary Outcomes (5)

• Progression Free Survival in Sub-Population in months

  42 months

• Progression Free Survival 2 in each group according to trial stratification factors

  58 months

• TFST (Time to First Subsequent Therapy)

  44 months

• TSST (Time to Second Subsequent Therapy)

  60 months

• Overall survival (OS)

  72 months

Study Arms (3)

A: triplet

EXPERIMENTAL

chemotherapy-free combination of niraprib + bevacizumab + Dostarlimab

Drug: Niraparib; Drug: Bevacizumab; Drug: TSR042

B: Doublet

EXPERIMENTAL

chemotherapy-free combination of niraparib + bevacizumab

Drug: Niraparib; Drug: Bevacizumab

C: standard of care

ACTIVE COMPARATOR

Standard of care chemotherapy: Carboplatin + paclitaxel

Drug: Carboplatin; Drug: Paclitaxel

Interventions

Niraparib DRUG

given orally once daily

Also known as: Zejula

A: triplet; B: Doublet

Bevacizumab DRUG

given as iv infusion every three weeks

Also known as: Avastin

A: triplet; B: Doublet

TSR042 DRUG

Given as IV infusion every three weeks

A: triplet

Carboplatin DRUG

given as iv infusion every three weeks

C: standard of care

Paclitaxel DRUG

given as iv infusion every three weeks

C: standard of care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer (platinum sensitivity defined as no recurrence within 6 months of last receipt of platinum/chemotherapy).
• High-grade serious or high-grade endometrioid histology or any histology with known BRCA mutation.
• Patient consents to perform BRCA test, and PD-L1 expression.
• Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
• No limits on number of platinum-based therapies.
• Up to one non-platinum-based line of therapy in recurrent setting is allowed.
• Patients may have received bevacizumab (or other anti-VEGF therapy) prior to entering in the trial.
• Patients may have participated in a PARP inhibitor maintenance trial or have received maintenance PARP inhibitor therapy are allowed, though it is necessary to unblind patient in order to correctly stratify. Patients who received a PARP inhibitor as definitive are not eligible. Patients may have participated in a trial containing immune-checkpoint inhibitor.
• Target group: Age 18+
• Histological confirmed ovarian, fallopian tube or peritoneal cancers
• Patients must give informed consent
• Patients may have undergone primary or interval debulking surgery
• Patients may have received bevacizumab or other anti-angiogenic therapy
• Patients may have received a PARP inhibitor as first-line maintenance therapy.
• Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria

You may not qualify if:

• Uncontrolled pulmonary embolism (PE)
• Deep venous thrombosis (DVT)
• Other related conditions, though patients with stable therapeutic anticoagulation for more than three months prior randomization are eligible for this study. This also apply to PE \& DVT.
• \. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months 13. History of clinically significant hemorrhage in the past 3 months 14. Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (Dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization) 15. Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure \> NYHA III, severe peripheral vascular disease, QT prolongation \>470 msec ,clinically significant pericardial effusion 16. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.
• \. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels 18. Active or chronic hepatitis C and/or B infection 19. Persistence of clinically relevant therapy related toxicity from previous chemotherapy 20. Proteinuria as demonstrated by: (a) urine protein: creatinine (UPC) ratio \>/= 1.0 at screening OR (b) urine dipstick for proteinuria \>/=2+ (patients discovered to have \>/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hr urine collection and must demonstrate \</=1g of protein in24 hours to be eligible 21. Patients must not have any known history of MDS 22. Patients must not have known persistent (\> 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy 23. Patients must not have known ≥ Grade 3 thrombocytopenia or anemia with the last chemotherapy regimen.

Sponsors & Collaborators

• Nordic Society of Gynaecological Oncology - Clinical Trials Unit: lead

Study Sites (8)

NSGO

Copenhagen, Region Sjælland, 2100, Denmark

Location

Rigshospitalet

Copenhagen, Region Sjælland, 2100, Denmark

Location

Rigshospitalet

København Ø, Region Sjælland, 2100, Denmark

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Tampere University Hospital

Tampere, Finland

Location

Haukeland University Hospital

Bergen, Haukeland, 5021, Norway

Location

Norwegian Radium Hospital

Oslo, 0310, Norway

Location

The Norwegian Radium Hospital

Oslo, 0310, Norway

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib; Bevacizumab; dostarlimab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• MANSOOR RAZA R MIRZA

  NSGO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, open-label, three arm study

Study Record Dates

• First Submitted: January 13, 2019
• First Posted: January 16, 2019
• Study Start: December 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2024
• Last Updated: July 15, 2021

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); NO (3); DK (4)