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Trial record 10 of 20 for:    parp inhibitor ovarian | Recruiting, Not yet recruiting, Available Studies

Study Evaluating the Efficacy of Maintenance Olaparib and Cediranib or Olaparib Alone in Ovarian Cancer Patients (ICON9)

This study is not yet open for participant recruitment.
Verified July 2017 by University College, London
Sponsor:
ClinicalTrials.gov Identifier:
NCT03278717
First Posted: September 12, 2017
Last Update Posted: September 12, 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):
University College, London
  Purpose
ICON 9 will assess the efficacy, safety and tolerability of maintenance olaparib in combination with cediranib compared to maintenance olaparib alone following a response to platinum-based chemotherapy in women with relapsed platinum-sensitive ovarian, fallopian tube or peritoneal cancer. Prognostic and predictive factors will be studied from tumour and blood samples.

Condition Intervention Phase
Ovarian Cancer Drug: Olaparib Drug: Cediranib Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: International Phase III Randomised Study to Evaluate the Efficacy of Maintenance Therapy With Olaparib and Cediranib or Olaparib Alone in Patients With Relapsed Ovarian Cancer Following a Response to Platinum-based Chemotherapy

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Progression free survival (PFS) measured from the date of randomisation to the date of objective progression (investigator assessed using RECIST v1.1) or date of death from any cause (in the absence of progression) [ Time Frame: 3 years ]
    Progression free survival (PFS) measured from the time of randomisation.

  • Overall survival (OS) measured from the date of randomisation to the date of death from any cause [ Time Frame: 3 years ]
    Overall survival (death from any cause) measured from the time of randomisation.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: 3 years ]
    Toxicity experienced by patients as assessed by the Common Terminology Criteria for Adverse Events v4.03

  • PFS and OS measured from the time of starting chemotherapy [ Time Frame: 3 years ]
    PFS and OS measured from the time of starting chemotherapy

  • Adherence to maintenance therapy- compliance and dose reductions and interruptions [ Time Frame: 3 years ]
    Adherence to maintenance therapy- compliance and dose reductions and interruptions

  • TSST (the time from randomisation to start of second subsequent therapy or death) [ Time Frame: 3 years ]
    TSST (the time from randomisation to start of second subsequent therapy or death)

  • Quality of life using EORTC QLQ C30 [ Time Frame: 3 years ]
    Quality of life using EORTC QLQ C30

  • Quality of life using EORTC QLQ OV28 [ Time Frame: 3 years ]
    Quality of life using EORTC QLQ OV28

  • Cost effectiveness using EQ-5D-5L for economic evaluation [ Time Frame: 3 years ]
    Cost effectiveness using EQ-5D-5L for economic evaluation

  • Progression free survival by CA125 - GCIG criteria [ Time Frame: 3 years ]
    Progression free survival by CA125 - GCIG criteria

  • VIII. Response rate (RECIST v1.1 and/or CA125) at 16 weeks of treatment in patients who had RECIST v1.1 measurable disease or elevated CA125 at randomisation. RECIST measurements will be based on investigator assessment not central review [ Time Frame: 3 years ]
    VIII. Response rate (RECIST v1.1 and/or CA125) at 16 weeks of treatment in patients who had RECIST v1.1 measurable disease or elevated CA125 at randomisation. RECIST measurements will be based on investigator assessment not central review


Estimated Enrollment: 618
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib and Cediranib

Patients will receive oral olaparib 300mg BD and oral cediranib 20mg OD.

Patients will attend hospital for a 2 weekly review for the first 8 weeks, then 4 weekly for year 1 and 8 weekly for year 2 onwards until discontinuation of all trial drugs. Treatment may continue beyond progression until the next line of treatment if the patient is deemed to still be deriving clinical benefit. QOL instruments will be collected at baseline, every clinic visit and continue to be completed after relapse.

Drug: Olaparib
Olaparib is a PARP inhibitor, targeting DNA repair processes.
Drug: Cediranib
Cediranib is an inhibitor of vascular endothelial growth factor-A (VEGF), targeting angiogenesis.
Active Comparator: Olaparib

Patients will receive oral olaparib 300mg BD.

Patients will attend hospital for a 2 weekly review for the first 8 weeks, then 4 weekly for year 1 and 8 weekly for year 2 onwards until discontinuation of all trial drugs. Treatment may continue beyond progression until the next line of treatment if the patient is deemed to still be deriving clinical benefit. QOL instruments will be collected at baseline, every clinic visit and continue to be completed after relapse.

Drug: Olaparib
Olaparib is a PARP inhibitor, targeting DNA repair processes.

Detailed Description:

ICON9 is an international multicentre randomised, phase III trial assessing maintenance treatment with olaparib and cediranib or olaparib alone in women with relapsed ovarian cancer whose disease progressed more than 6 months after first line chemotherapy. Women whose disease responds to platinum chemotherapy following 3 to 4 cycles can be registered for collection of germline BRCA test results if known, and somatic BRCA testing of archival tumour specimens or secondary debulking tissue if required. Patients who have completed treatment and whose disease has responded (partial or complete) to a minimum of 4 cycles of platinum based chemotherapy will be randomised to maintenance treatment of either olaparib and cediranib or olaparib alone.

The maintenance regimen may be continued beyond radiological progression until trial closure if the patient is deemed to still be deriving clinical benefit, but must be discontinued once subsequent treatment is instituted.

  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

Registration Inclusion Criteria:

  1. Provision of informed consent prior to any study specific procedures and the ability to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
  2. Females aged ≥ 18 years with previous histologically proven diagnosis of high grade serous or endometrioid carcinoma of the

    • Ovary
    • Fallopian tube
    • or peritoneum, progressing >6 months after day 1 of the last cycle of first-line platinum-based chemotherapy and requiring treatment with platinum-based chemotherapy on the basis of radiological evidence of disease or following surgical resection of recurrent disease.

    Patients may be included post-secondary surgery if undertaken >6 months after day 1 of the last cycle of first-line platinum-based chemotherapy.

  3. Patients must have had CT or MRI proven relapsed disease (measureable by RECIST 1.1 or non-measureable abnormalities supported by GCIG CA125 criteria of progression), or have had debulking surgery for first relapse.
  4. Patients showing response to chemotherapy mid-treatment (post 3 or 4 cycles), either by GCIG CA125 criteria or 'partial response' on CT/MRI scan, or no evidence of progression having undergone surgical debulking, should be approached for ICON9 trial registration to allow for BRCA mutation status to be assessed (germline and/or somatic).
  5. Prior front-line maintenance therapy with bevacizumab is permitted.
  6. ECOG performance status 0-1.
  7. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer or from secondary debulking surgery must be available for central testing. For inclusion in i) the genetic HRD Test and ii) the biomarker research, patients must complete the appropriate consent form.
  8. Patients must have a life expectancy ≥ 16 weeks.
  9. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days prior to study treatment and confirmed prior to treatment on day 1.

    Postmenopausal is defined as age ≥60 years, or:

    • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
    • Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
    • Radiation-induced oophorectomy with last menses >1 year ago
    • Chemotherapy-induced menopause with >1 year interval since last menses
    • Surgical sterilisation (bilateral oophorectomy or hysterectomy)
  10. Adequately controlled blood pressure (systolic blood pressure [SBP] ≤140 mmHg; diastolic blood pressure [DBP] ≤ 90mmHg) on maximum of 2 antihypertensive medications.
  11. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction.

Randomisation Inclusion Criteria:

  1. Patients must have received at least 4 cycles, and a maximum of 6 cycles of second-line platinum-based chemotherapy.
  2. In patients with measurable disease end of treatment scans must have a RECIST 1.1 'partial response' or 'complete response' for randomisation to take place.
  3. In patients with non-measurable disease, who have not undergone debulking surgery, there must have been a GCIG CA125 response to chemotherapy.
  4. If CA125 has not normalised after chemotherapy then patients must have no evidence of disease progression by GCIG criteria.
  5. Patients who have had debulking surgery at first relapse must have no evidence of disease progression on imaging (CT or MRI) and by GCIG CA125 criteria.
  6. Expected to be able to commence treatment within 7 days of post randomisation, and within 4-8 weeks post day 1 of the last cycle of chemotherapy.
  7. Adequate bone marrow function as defined below:

    • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/l
    • Platelet (Plt) ≥ 100 x 109/l
    • Haemoglobin (Hb) ≥ 100g/l required and no packed blood transfusions in the 14 days prior to starting trial treatment
  8. Adequate liver function as defined below:

    • Serum bilirubin ≤ 1.5 x ULN (or ≤ 3 for cases of known Gilbert's syndrome)
    • Serum transaminases ≤3 x ULN
    • Serum transaminases ≤ 5 x ULN if liver metastasis present
  9. Adequate renal function as defined below:

    • Serum creatinine ≤ 1.5 x ULN and calculated glomerular filtration rate (GFR) ≥50ml/min (calculated as per local practice)

  10. Germline and/or somatic BRCA mutation status must be known prior to randomisation. See section 6.4.2
  11. Urine protein:creatinine ratio (UPC) ≤1 OR ≤2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have UPC <0.5 on 2 consecutive samples.

Exclusion Criteria:

  1. Non-epithelial ovarian cancer, carcinosarcoma, clear cell carcinoma and mucinous carcinomas.
  2. Arterial thrombotic event (including transient ischemic attack, cerebrovascular accident, and peripheral arterial embolus) within the last 12 months.
  3. Patients unable to swallow orally administered medication and patients with gastrointestinal impairment that could affect ability to take, or absorption of oral medicines including sub-acute or complete bowel obstruction.
  4. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment.
  5. History of intra-abdominal abscess within 3 months prior to starting treatment.
  6. 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.
  7. Symptomatic or clinically significant inflammatory bowel disease (Crohn's disease or ulcerative colitis).
  8. Patients with an ileostomy will be excluded.
  9. Evidence of severe or uncontrolled cardiac disease.

    1. Myocardial infarct or unstable angina within the last 6 months
    2. New York Health Association (NHYA) ≥ grade 2 congestive heart failure
    3. Cardiac ventricular arrhythmias requiring medication
    4. History of 2nd or 3rd degree atrioventricular conduction defects
  10. Resting ECG with QTcF > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  11. Evidence of active bleeding or bleeding diathesis.

    Significant haemorrhage of >30ml in a single episode within the last 3 months or any haemoptysis (>5ml fresh blood in last 4 weeks).

  12. Malignancy treated within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage 1, grade 1 endometrial carcinoma.
  13. Previous treatment with VEGFR tyrosine kinase inhibitors or PARP inhibitors are not permitted.
  14. Patients with a known hypersensitivity to excipients of cediranib or olaparib.
  15. Persisting ≥ grade 2 CTCAE toxicity (except alopecia and neuropathy) from previous anti-cancer treatment.
  16. Major surgery within 14 days before anticipated start of treatment and patients must have recovered from any effects of major surgery.
  17. Inability to attend or comply with treatment or follow-up scheduling.
  18. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicated the use of an investigation drug or puts the patients at high risk for treatment-related complications.
  19. Pregnant or breast-feeding women are excluded. Women of childbearing potential will be excluded unless effective methods of contraception are used from signing of the informed consent, throughout the period of taking study treatment and for at least 6 weeks after last dose of trial drug(s).
  20. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
  21. Concomitant use of known CYP3A4 inhibitors (such as ketoconazole, itraconazole, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir, telithromycin and clarithromycin or moderate CYP3A inhibitors (e.g. Ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  22. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  23. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
  24. Other psychological, psychiatric, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
  25. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  26. Immunocompromised patients e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
  27. Patients with symptomatic uncontrolled brain or meningeal metastases. A scan to confirm the absence of brain metastases is not required. 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.
  28. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  29. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  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): NCT03278717


Contacts
Contact: Gita Parmar +44 (0)20 7679 9114 ctc.ICON9@ucl.ac.uk
Contact: Mandy Feeney +44 (0)20 7679 9890 ctc.ICON9@ucl.ac.uk

Sponsors and Collaborators
University College, London
  More Information

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT03278717     History of Changes
Other Study ID Numbers: UCL/14/0795
First Submitted: July 31, 2017
First Posted: September 12, 2017
Last Update Posted: September 12, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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