Clinical Trials /

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

NCT02889900

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: D8488C00001
  • NCT ID: NCT02889900

Conditions

  • Recurrent Platinum Resistant Ovarian Cancer

Interventions

DrugSynonymsArms
cediranib and olaparibOlaparib: also known as Lynparzacombination of cediranib and olaparib

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.

Detailed Description

      The study will recruit approximately 60 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 primary analysis, approximately 8 months after
      enrollment of the last patient.
    

Trial Arms

NameTypeDescriptionInterventions
combination of cediranib and olaparibExperimentalOpen label
  • cediranib and olaparib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:% 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

Measure: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)
Safety Issue:
Description:% 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
Measure: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)
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description:% of patients who have a best overall response of CR or PR or SD (at 6 months)
Measure: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)
Safety Issue:
Description:the time from the date of first dose until death due to any cause
Measure: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)
Safety Issue:
Description:the time from the date of first dose of IPs to the earlier of the date of discontinuation of both IPs, or death date
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • ovarian cancer

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