Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 30 of 598 for:    Recruiting, Not yet recruiting, Available Studies | Ovarian cancer

Trial Comparing Niraparib-bevacizumab-TSR042 and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03806049
Recruitment Status : Not yet recruiting
First Posted : January 16, 2019
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Nordic Society for Gynaecologic Oncology

Brief Summary:
NSGO / AVANOVA-Triplet: This three-arm randomized trial is to demonstrate efficacy of niraparib-bevacizumab-TSR-042 triplet combination against standard of care treatment and to demonstrate efficacy of niraparib-bevacizumab-TSR-042 triplet combination against niraparib-bevacizumab doublet combination for patients with platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Niraparib Drug: Bevacizumab Drug: TSR042 Drug: Carboplatin Drug: Paclitaxel Phase 3

Detailed Description:
This is a multicenter randomized open-label trial to compare two different chemotherapy-free arms against standard of care treatment in patients with recurrent ovarian cancer with >6 months of chemotherapy-free interval to prior therapy.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 337 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, open-label, three arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ENGOT-OV42-NSGO/AVANOVA-Triplet: A Randomized Study to Evaluate the Efficacy of Niraparib-bevacizumab-TSR042 Triplet Against Niraparib-bevacizumab Doublet and Against Standard of Care in Women With Platinum-sensitive Ovarian Cancer
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2024


Arm Intervention/treatment
Experimental: A: triplet
chemotherapy-free combination of niraprib + bevacizumab + TSR042
Drug: Niraparib
given orally once daily
Other Name: Zejula

Drug: Bevacizumab
given as iv infusion every three weeks
Other Name: Avastin

Drug: TSR042
Given as IV infusion every three weeks

Experimental: B: Doublet
chemotherapy-free combination of niraparib + bevacizumab
Drug: Niraparib
given orally once daily
Other Name: Zejula

Drug: Bevacizumab
given as iv infusion every three weeks
Other Name: Avastin

Active Comparator: C: standard of care
Standard of care chemotherapy: Carboplatin + paclitaxel
Drug: Carboplatin
given as iv infusion every three weeks

Drug: Paclitaxel
given as iv infusion every three weeks




Primary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 42 months ]
    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.


Secondary Outcome Measures :
  1. Progression Free Survival in Sub-Population in months [ Time Frame: 42 months ]
    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 for the predefined study subgroups.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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).
  2. High-grade serious or high-grade endometrioid histology or any histology with known BRCA mutation.
  3. Patient consents to perform BRCA test, and PD-L1 expression.
  4. Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
  5. No limits on number of platinum-based therapies.
  6. Up to one non-platinum-based line of therapy in recurrent setting is allowed.
  7. Patients may have received bevacizumab (or other anti-VEGF therapy) prior to entering in the trial.
  8. 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.
  9. Target group: Age 18+
  10. Histological confirmed ovarian, fallopian tube or peritoneal cancers
  11. Patients must give informed consent
  12. Patients may have undergone primary or interval debulking surgery
  13. Patients may have received bevacizumab or other anti-angiogenic therapy
  14. Patients may have received a PARP inhibitor as first-line maintenance therapy.
  15. Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria
  16. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
  17. ECOG performance status 0-2
  18. Adequate organ function

    1. Absolute neutrophil count (ANC) ≥1,5 x 109/L
    2. Platelets >100 x 109/L
    3. Hemoglobin ≥ 9g/dl
    4. Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula
    5. Total bilirubin ≤1.5x ULN
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  19. Able to take oral medications
  20. Life expectancy of at least 12 weeks
  21. Patients must fulfill all inclusions criteria and according to investigator fit to receive niraparib, bevacizumab and TSR042.
  22. Women of childbearing potential must use adequate birth control for the duration of study participation -

Exclusion Criteria:

Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers and cancer types not mentioned in the inclusion criteria 2. Concurrent cancer therapy 3. Concurrent treatment with an investigational agent or participation in another clinical trial 4. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period 5. Previous malignant disease: patients are not eligible for the study if diagnosis, detection or treatment of invasive cancer (other than ovarian cancer; with the exception of basal or squamous cell carcinoma of the skin that was definitively treated) was detected within 2 years prior to randomization 6. Active infections or other serious underlying significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study 7. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug 8. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction 9. Known contraindications to PARP inhibitors, VEGF directed therapy or immune checkpoint inhibitors 10. Known uncontrolled hypersensitivity to the investigational drugs 11. History of major thromboembolic event defined as:

  • 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.

    12. 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.

    17. 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.


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): NCT03806049


Contacts
Layout table for location contacts
Contact: Mansoor R Mirza, MD 35459624 mansoor@rh.regionh.dk

Locations
Layout table for location information
Denmark
NSGO
Copenhagen, Sjaelland, Denmark, 2100
Rigshospitalet
Copenhagen, Sjaelland, Denmark, 2100
Rigshospitalet
København Ø, Sjaelland, Denmark, 2100
Aalborg University Hospital
Aalborg, Denmark, 9000
Finland
Tampere University Hospital
Tampere, Finland
Norway
Haukeland University Hospital
Bergen, Haukeland, Norway, 5021
Norwegian Radium Hospital
Oslo, Norway, 0310
The Norwegian Radium Hospital
Oslo, Norway, 0310
Sponsors and Collaborators
Nordic Society for Gynaecologic Oncology
Investigators
Layout table for investigator information
Study Chair: MANSOOR RAZA R MIRZA NSGO

Layout table for additonal information
Responsible Party: Nordic Society for Gynaecologic Oncology
ClinicalTrials.gov Identifier: NCT03806049     History of Changes
Other Study ID Numbers: NSGO/AVANOVA-Triplet
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All individual participant data will be anonymized

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nordic Society for Gynaecologic Oncology:
chemotherapy-free regimen
niraparib
bevacizumab
TSR042
recurrent ovarian cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Paclitaxel
Bevacizumab
Carboplatin
Niraparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs