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To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer (ORZORA)

This study is currently recruiting participants.
Verified October 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02476968
First Posted: June 22, 2015
Last Update Posted: October 5, 2017
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.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
This is a prospective, open-label, single arm, multi-center study to assess the real world clinical effectiveness and safety of olaparib maintenance monotherapy as the capsule formulation (in line with the EU approved prescribing information) and will be conducted in platinum-sensitive relapsed high grade epithelial ovarian cancer patients (including patients with primary peritoneal and / or fallopian tube cancer) who carry germline or somatic BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious [known or predicted to be detrimental/lead to loss of function]).

Condition Intervention Phase
BRCA or HRR+ Mutated Ovarian Cancer Patients Drug: Olaparib Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open Label, Single Arm, Multicentre Study to Assess the Clinical Effectiveness and Safety of Lynparza (Olaparib) Capsules Maintenance Monotherapy in Platinum Sensitive Relapsed Somatic or Germline BRCA Mutated Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy (ORZORA).

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Time from study enrolment to disease progression (assessed according to RECIST 1.1 guidelines) or death. [ Time Frame: Time from first patient enrolled to data cut off (up to 32 months) assessed approximately every 12 weeks ]
    • To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed progression free survival (PFS) according to modified Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 in patients with sBRCAm ovarian cancer.
    • To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed PFS according to RECIST 1.1 in patients with BRCAm ovarian cancer.


Secondary Outcome Measures:
  • Time to death and Time to second progression event or death if this occurs before second progression event. [ Time Frame: Time from first patient enrolled to data cut off (up to 32 months) ]

    To assess the real world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer, by assessment of:

    1. Overall survival,
    2. Time to investigator-assessed second progression or death.

  • Time to first and second treatment commencement or death and time to olaparib discontinuation or death. [ Time Frame: Time from first patient enrolled to first & second treatment commencement or death and time to olaparib discontinuation or death analysed at data cut off (up to 32 months) ]

    To assess the real world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer, by assessment of :

    1. time to first subsequent therapy or death,
    2. time to second subsequent therapy or death and,
    3. time to olaparib discontinuation or death.

  • Functional Assessment of Cancer Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and ORZORA QoL Additional Items Questionnaire [ Time Frame: Time from first patient enrolled to 24 months or the data cut off for the primary analysis, whichever comes first. ]
    To assess and describe the quality of life (QoL) of patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer.

  • Safety summary tables, Functional Living Index-Emesis (FLIE) Questionnaire, and concomitant medication use. [ Time Frame: Time from first patient enrolled to 24 months or the data cut off for the primary analysis, whichever comes first. ]

    To describe patterns of routine clinical use of olaparib, the nature and patterns of adverse events (AEs) of nausea and vomiting and their impact on QoL in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer.

    To describe nausea/vomiting toxicity management patterns used in routine clinical practice.



Other Outcome Measures:
  • AEs/Serious adverse events (SAEs)/AE of special interest (AESI) [ Time Frame: From time of signature of informed consent to 30 days after last dose ]
    To assess the safety and tolerability of olaparib maintenance monotherapy in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer.


Estimated Enrollment: 275
Actual Study Start Date: September 28, 2015
Estimated Study Completion Date: June 3, 2019
Estimated Primary Completion Date: June 3, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Olaparib
Open Label Drug
Drug: Olaparib

Olaparib Capsule - 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage.

Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily.

Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water.

Other Name: Lynparza

Detailed Description:

The study will recruit approximately 250 patients with sBRCAm disease or gBRCAm disease, with the aim to accrue a minimum of 50 patients with sBRCAm disease.

Patients with an unknown germline BRCA mutated status or gBRCAwt disease or previously identified as having a BRCAm disease by a tumour test will be considered for screening and will undergo, upon informed consent signature, central tumor and blood testing to determine their BRCA mutation status. In addition to central BRCA testing, patients screened for the study with unknown BRCA status or with known gBRCAwt status, for whom an adequate archival tumour tissue sample is available, will be tested for qualifying HRR gene alterations. Patients confirmed to carry a deleterious or suspected deleterious BRCA-independent genetic alteration in any of 13 genes involved in the Homologous Recombination Repair (HRR) pathway (HRRm cohort) will be allowed into an additional exploratory cohort (HRRm cohort). It is expected that approximately 25 patients will be included in the HRRm cohort before the target number of 250 patients with BRCAm disease is reached.

Patients will be assigned olaparib capsules orally 400 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion) and will be assessed every 4 weeks whilst on treatment.

All patients will have clinical and objective radiological tumour assessments according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator's opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety.

For exploratory analysis purposes, patients will be asked to provide consent to:

  1. Optional tumour samples at baseline and at disease progression
  2. An optional blood sample only for patients with a confirmed sBRCAm or HRRm disease
  Eligibility

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.


Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent prior to any study specific procedures
  2. Age 18 years or over
  3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) [Genetic counselling for patients with germline BRCA mutations should be performed according to local regulations] Or Tumour BRCAwt status and documented qualifying mutation in any of 13 genes involved in the HRR pathway, excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1,CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D,and RAD54L), identified by the Lynparza HRR Assay in archival tumour tissue (i.e.,BRCA-independent HRRm)
  4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer):

    − Platinum sensitive disease is defined as disease progression ≥6 months after completion of their last dose of platinum based chemotherapy

  5. Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment:

    − For the last chemotherapy course immediately prior to enrolment on the study, patients must be, in the opinion of the investigator, in response (partial or complete radiological response) and no evidence of a rising CA-125, following completion of this chemotherapy course.

  6. Patients must have normal organ and bone marrow function measured within 28 days of enrolment, as defined below:

    • Haemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
  7. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase [SGOT]) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase [SGPT]) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5x ULN
  8. Creatinine clearance > 50 ml/min (calculated)
  9. Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential.

Postmenopausal is defined as any of the following:

  • Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments
  • For women under 50 years old, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range
  • Radiation-induced oophorectomy, with interval of 1 year or more since last menses
  • Chemotherapy-induced menopause, with interval of 1 year or more since last menses
  • Surgical sterilisation (bilateral oophorectomy or hysterectomy).

Exclusion Criteria:

  1. Patients previously diagnosed with gBRCAm disease
  2. Participation in another clinical study with an investigational product during the most recent chemotherapy course
  3. Patients with a known hypersensitivity to olaparib or any of the excipients of the product
  4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia
  6. Patients with myelodysplastic syndrome/acute myeloid leukaemia
  7. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C
  8. Patients with symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days
  9. Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection
  10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.
  Contacts and Locations
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): NCT02476968


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 80 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Sandro Pignata, Doctor of Medicine Istituto Nazionale Tumori Fondazione G. Pascale, 80131, Napoli, Italy
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02476968     History of Changes
Other Study ID Numbers: D0816C00012
First Submitted: June 10, 2015
First Posted: June 22, 2015
Last Update Posted: October 5, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents