Trial record 12 of 25 for:    parp inhibitor ovarian | Open Studies

Niraparib and/or Niraparib-Bevacizumab Combination Against Bevacizumab Alone in HRD Platinum Sensitive Ovarian Cancer (AVANOVA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Nordic Society for Gynaecologic Oncology
Sponsor:
Collaborators:
ENGOT
GCIG
University of Utah
Massachusetts General Hospital
Dana-Farber Cancer Institute
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Nordic Society for Gynaecologic Oncology
ClinicalTrials.gov Identifier:
NCT02354131
First received: January 25, 2015
Last updated: January 14, 2016
Last verified: January 2016
  Purpose

Part 1 (Phase 1): safety and tolerability of bevacizumab-Niraparib combination Part 2 (Randomized Phase 2): to compare Progression-Free Survival (PFS)

PARP inhibitors are active as monotherapy to treat patients with recurrent ovarian cancer; the strongest activity being observed in the platinum sensitive, gBRCAmut subgroup as well as in gBRCAwt, HRD population.

In the same population there is level one evidence that bevacizumab is beneficial. And a phase two randomized study has indicated that combination of a PARP inhibitor with anti-angiogenic drug is superior to PARP inhibitor alone.

The questions are:

Is single agent PARP inhibitor, niraparib superior to bevacizumab? Is niraparib combined with bevacizumab superior to bevacizumab? Is niraparib-bevacizumab combination superior to sequential bevacizumab followed by niraparib? The comparison of tolerability and efficacy of niraparib-bevacizumab combination against sequential bevacizumab and niraparib.


Condition Intervention Phase
Ovarian Cancer
Drug: Niraparib
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: AVANOVA1 - Phase I of Bevacizumab-Niraparib Combination. AVANOVA2 -A 3-arm, Phase II Randomized Study of Niraparib &/or Niraparib-bevacizumab Combination Against Bevacizumab Alone in HRD Platinum-sensitive Epithelial Ovarian Cancer.

Resource links provided by NLM:


Further study details as provided by Nordic Society for Gynaecologic Oncology:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    This is pick the winer trial. The best arm will be used for phase 3 trial against standard of care.


Secondary Outcome Measures:
  • Disease Control Rate [ Time Frame: 30 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 147
Study Start Date: February 2015
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequential Bevacizumab - Niraparib
bevacizumab monotherapy - upon PD Niraparib monotherapy
Drug: Niraparib
Sequential bevacizumab followed by Niraparib versus Niraparib versus Bevacizumab-Niraparib combo
Other Name: Bevacizumab
Drug: Bevacizumab
Experimental: Niraparib monotherapy
Niraparib monotherapy
Drug: Niraparib
Sequential bevacizumab followed by Niraparib versus Niraparib versus Bevacizumab-Niraparib combo
Other Name: Bevacizumab
Experimental: Niraparib-bevacizumab combination
Niraparib-bevacizumab combination therapy until progression
Drug: Niraparib
Sequential bevacizumab followed by Niraparib versus Niraparib versus Bevacizumab-Niraparib combo
Other Name: Bevacizumab
Drug: Bevacizumab

Detailed Description:

Part 1: This is a single-centre, phase 1a, open-label, dose-escalation study to evaluate the safety and tolerability of bevacizumab-niraparib combination and determine the RP2D in patients with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The standard 3+3 design will be used. Part 2: (n=132) This multicenter, prospective, open-label, randomized phase 2 study is evaluating the efficacy of niraparib and/or niraparib-bevacizumab combination against bevacizumab alone in Women with Homologous Recombination Deficient (HRD), platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Patients on bevacizumab are switched over to receive single agent niraparib upon progression of disease. This subgroup receiving sequential bevacizumab and niraparib will be compared for efficacy against combination arm.

Stratification: Patients are stratified according to:

  1. BRCA status: BRCA mutated vs. non-carrier
  2. Prior receipt of anti-angiogenic therapy (yes/no) Randomization: 1:1:1 randomization

Study arms: Patients are randomized to one of the three treatment arms:

  • Arm A: (comparator) bevacizumab monotherapy until progression. Upon progression these patients switched to niraparib monotherapy until second progression
  • Arm B: (experimental arm): Niraparib monotherapy until progression
  • Arm C: (experimental arm): Niraparib-bevacizumab combination therapy until progression
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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. Other histological types are allowed if documented BRCA mutation.
  3. Patient consents to perform HRD test.
  4. HRD test positive.
  5. Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.

    • No limits on number of platinum-based therapies. Population of patients who has previously received ≥ 3 lines of therapy for relapsed disease will be capped at 40%.
    • Up to one non-platinum-based line of therapy in recurrent setting
    • Patients who are treated with bevacizumab just prior to entering in the trial must not have progressed under or within 3 months after bevacizumab
  6. Histological confirmed ovarian, fallopian tube or peritoneal cancers
  7. Patients must give informed consent
  8. Patients may have undergone primary or interval debulking surgery
  9. Patients may have received bevacizumab or other anti-angiogenic therapy
  10. Patients must have disease that is measurable according to RECIST or assessable according to the GCIG CA-125 criteria
  11. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
  12. ECOG performance status 0-2
  13. Adequate organ function Absolute neutrophil count (ANC) ≥1,5 x 109/L Platelets >100 x 109/L Hemoglobin ≥ 9g/dl Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula Total bilirubin ≤1.5x ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  14. Able to take oral medications
  15. Life expectancy of at least 12 weeks
  16. Patients must be fit to receive niraparib and/or bevacizumab
  17. Women of childbearing potential must use adequate birth control for the duration of study participation

Exclusion Criteria:

  1. 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. Prior treatment with PARP inhibitors
  5. 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
  6. 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
  7. 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
  8. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
  9. 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
  10. Known contraindications to PARP inhibitors or VEGF directed therapy
  11. Known uncontrolled hypersensitivity to the investigational drugs
  12. 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

  13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months
  14. History of clinically significant hemorrhage in the past 3 months
  15. 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)
  16. 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
  17. 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.
  18. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels
  19. Active or chronic hepatitis C and/or B infection
  20. Persistence of clinically relevant therapy related toxicity from previous chemotherapy
  21. 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
  22. Patients must not have any known history of MDS
  23. Patients must not have known persistent (> 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02354131

Contacts
Contact: Mansoor R Mirza, MD +45 35453311 mansoor@rh.regionh.dk
Contact: Louisa Boufercha, MA +45 35453311 louisa.boufercha@regionh.dk

Locations
Denmark
Rigshospitalet Recruiting
Copenhagen, Sjaelland, Denmark, 2100
Sponsors and Collaborators
Nordic Society for Gynaecologic Oncology
ENGOT
GCIG
University of Utah
Massachusetts General Hospital
Dana-Farber Cancer Institute
Myriad Genetics, Inc.
Investigators
Study Chair: Mansoor R Mirza, MD Nordic Society for Gynaecologic Oncology
  More Information

Responsible Party: Nordic Society for Gynaecologic Oncology
ClinicalTrials.gov Identifier: NCT02354131     History of Changes
Other Study ID Numbers: ENGOT-OV24-NSGO/AVANOVA 
Study First Received: January 25, 2015
Last Updated: January 14, 2016
Health Authority: Denmark: Danish Health and Medicines Authority

Keywords provided by Nordic Society for Gynaecologic Oncology:
Ovarian cancer
Niraparib
Bevacizumab
PARP
Phase 2 randomized

Additional relevant MeSH terms:
Ovarian Neoplasms
Ovarian Diseases
Angiogenesis Inhibitors
Growth Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Niraparib
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016