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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 not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2016 by AstraZeneca
Sponsor:
Collaborator:
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02889900
First received: July 20, 2016
Last updated: August 31, 2016
Last verified: August 2016
  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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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) ] [ Designated as safety issue: No ]

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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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
Study Start Date: September 2016
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (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 chemotherapy, and who do not carry a deleterious or suspected deleterious germline BRCA mutation. All patients should have recurrent platinum resistant disease. All patients should have received prior antiangiogenic treatment e.g. bevacizumab, either in a first line or a 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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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 radiological evidence of disease recurrence within 6 months of the last receipt of platinum-based chemotherapy. Patients with platinum refractory disease are not eligible
  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 e.g. bevacizumab in first line or recurrent setting
  9. At least three prior lines of chemotherapy for advanced ovarian cancer. Only one prior non-platinum treatment is allowed
  10. Confirmation of the availability tumor sample from the primary or recurrent cancer must be provided
  11. Patients must have adequate organ and 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. Exposure to any IP during the last 30 days or 5 half-lives (whichever is longer), prior to enrollment
  2. Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi
  3. 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
  4. Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease
  5. 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
  6. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
  7. History of intra-abdominal abscess within 3 months prior to starting treatment
  8. 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
  9. Other malignancy within the last 5 years
  10. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
  11. Central nervous system metastases
  12. 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
  13. 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
  14. History of stroke or transient ischemic attack within 6 months
  15. Uncontrolled intercurrent illness
  16. Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
  17. Concomitant use of known strong and moderated CYP3A4 inhibitors and inducers
  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: 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

Locations
United States, California
Research Site Not yet recruiting
Greenbrae, California, United States
Research Site Not yet recruiting
Los Angeles, California, United States
Research Site Not yet recruiting
Orange, California, United States
Research Site Not yet recruiting
San Diego, California, United States
United States, Florida
Research Site Not yet recruiting
Orlando, Florida, United States
United States, Kansas
Research Site Not yet recruiting
Westwood, Kansas, United States
United States, Louisiana
Research Site Not yet recruiting
Covington, Louisiana, United States
United States, Maryland
Research Site Not yet recruiting
Bethesda, Maryland, United States
United States, Missouri
Research Site Not yet recruiting
Kansas City, Missouri, United States
United States, Ohio
Research Site Not yet recruiting
Columbus, Ohio, United States
United States, South Dakota
Research Site Not yet recruiting
Siouxfalls, South Dakota, United States
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 
Study First Received: July 20, 2016
Last Updated: August 31, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 26, 2016