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Trial record 4 of 17 for:    CONCERTO

Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer (CONCERTO)

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02889900
First Posted: September 7, 2016
Last Update Posted: December 4, 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.
Collaborator:
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
This is an open label, single arm, multi-center study to assess the efficacy and safety of the combination of cediranib and olaparib tablets in platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma patients who have received at least 3 prior lines of chemotherapy and who do not carry deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutations.

Condition Intervention Phase
Recurrent Platinum Resistant Ovarian Cancer Drug: cediranib and olaparib Phase 2

An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Objective response rate (ORR) by independent central review (ICR), using RECIST version 1.1. [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    % of patients with measurable disease at baseline, with at least one visit response of CR or PR that is confirmed at least 4 weeks later


Secondary Outcome Measures:
  • ORR by investigator assessment using RECIST 1.1 [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    % of patients with measurable disease at baseline, with at least one visit response of CR or PR that is confirmed at least 4 weeks later

  • Duration of response (DoR) assessment using RECIST 1.1 [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression

  • Progression free survival (PFS) assessment using RECIST 1.1 [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    the time from date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression

  • Disease control rate (DCR) assessment using RECIST 1.1 [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    % of patients who have a best overall response of CR or PR or SD (at 6 months)

  • Overall survival (OS) [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    the time from the date of first dose until death due to any cause

  • Time to discontinuation or death (TDT) [ Time Frame: from first patient enrolled to data cut off (8 months after the last patient has received her first dose of IP) ]
    the time from the date of first dose of IPs to the earlier of the date of discontinuation of both IPs, or death date

  • Evaluate quality of life using European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire [ Time Frame: from baseline to 30 days after last dose ]

Other Outcome Measures:
  • Adverse events (AEs), and treatment emergent changes in vital signs and laboratory parameters. [ Time Frame: from time of signature of informed consent to 30 days after last dose ]
    To evaluate the safety and tolerability of the combination of cediranib and olaparib.

  • Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO CTCAE™) [ Time Frame: from baseline to 30 days after last dose ]
    To assess adverse events by patient self reporting of specific Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) symptoms.


Estimated Enrollment: 100
Actual Study Start Date: January 17, 2017
Estimated Study Completion Date: June 7, 2019
Estimated Primary Completion Date: June 7, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combination of cediranib and olaparib
Open label
Drug: cediranib and olaparib

Cediranib tablets oral dose 30 mg once daily; Olaparib(Lynparza) tablet 200 mg twice daily

Dose reduction for both products is allowed

Other Name: Olaparib: also known as Lynparza

Detailed Description:

The study will recruit approximately 100 patients aged ≥18 years, with histologically proven diagnosis of platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma who have received at least 3 prior lines of therapy, and who do not carry a deleterious or suspected deleterious germline BRCA mutation. All patients should have recurrent platinum resistant disease. The receipt of prior antiangiogenic treatment (e.g. bevacizumab) is optional. If used, it can be in the first line or recurrent setting. To be eligible to enter the study, all patients should have measurable disease (as assessed by the Investigator).

There is no maximum duration for taking the study treatments (cediranib+olaparib). Patients should continue on study treatments until objective radiological disease progression, as defined by RECIST version 1.1 guidelines, or they meet other discontinuation criteria. Following discontinuation of study treatment patients will be followed for disease progression (if they have not already progressed), survival and post-progression anti cancer therapies until the data cut-off for the final OS analysis, approximately 12 months after enrolment of the last patient.

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Ability and willingness to provide written informed consent, and to comply with the requirements of the protocol
  2. Females aged ≥18 years with previous histologically proven diagnosis of high grade serous, high grade endometroid or clear cell ovarian cancer, fallopian tube or primary peritoneal carcinoma
  3. No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes
  4. Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy
  5. CT/MRI evidence of measurable disease as per RECIST 1.1 defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) and which is suitable for accurate repeated measurements
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  7. Life expectancy ≥12 weeks
  8. Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
  9. At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol
  10. Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided
  11. Patients must have adequate organ and bone marrow function
  12. Adequately controlled blood pressure
  13. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
  14. Able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
  15. Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of IPs

Exclusion Criteria:

  1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  2. Previous enrollment in the present study.
  3. Exposure to any IP during the last 4 weeks prior to enrollment.
  4. Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi
  5. Recent cancer-directed therapies: Radiotherapy (RT) within 4 weeks, chemotherapy or other systemic anti-cancer therapy within 4 weeks, or prior anti-angiogenic treatment (e.g., bevacizumab) within 6 weeks prior to starting treatment
  6. Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease
  7. Major surgical procedure within 2 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
  8. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
  9. History of intra-abdominal abscess within 3 months prior to starting treatment
  10. History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula
  11. Other malignancy within the last 5 years
  12. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
  13. Central nervous system metastases
  14. Patients with any of the following: History of myocardial infarction within 6 months prior to starting treatment; Unstable angina; Resting electrocardiogram (ECG) with clinically significant abnormal findings; New York Heart Association functional classification of III or IV
  15. Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per institutional guidelines, or <55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors: Prior treatment with anthracyclines; Prior treatment with trastuzumab; Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT; History of myocardial infarction within 6-12 months prior to start of IPs; Prior history of other significant impaired cardiac function
  16. History of stroke or transient ischemic attack within 6 months
  17. Uncontrolled intercurrent illness
  18. Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
  19. No prior allogenic bone marrow transplant or double umbilical cord blood transplantation
  20. Known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection on antiviral treatment
  21. Concomitant use of known strong or moderate CYP3A inhibitors
  22. Concomitant use of known strong or moderate CYP3A inducers
  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): NCT02889900


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Tsveta Milenkova, M.D. Tsveta.Milenkova@astrazeneca.com

  Show 46 Study Locations
Sponsors and Collaborators
AstraZeneca
Myriad Genetic Laboratories, Inc.
Investigators
Principal Investigator: Jung-Min Lee, M.D. NIH - National Cancer Institute
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02889900     History of Changes
Other Study ID Numbers: D8488C00001
First Submitted: July 20, 2016
First Posted: September 7, 2016
Last Update Posted: December 4, 2017
Last Verified: November 2017

Keywords provided by AstraZeneca:
ovarian cancer

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
Cediranib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors