| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| High grade serous or endometrioid ovarian, fallopian and peritoneal cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ovarian, fallopian and peritoneal cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033128 |
| E.1.2 | Term | Ovarian cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| ICON9 is a research study investigating patients with recurrent ovarian, fallopian tube or primary peritoneal cancer, who have had their tumour shrunk by chemotherapy. We are investigating whether we can increase the effectiveness of ovarian cancer treatment by adding one or two new anti-cancer drugs: cediranib and olaparib. We want to determine if by combining cediranib and olaparib as a maintenance therapy, we can effectively control the regrowth of ovarian cancer following a good response to chemotherapy. Maintenance therapy in ICON9 is given to a patient to prolong the time between chemotherapy treatments. The primary study endpoints are progression free survival (the length of time during and after the treatment that a patient lives with cancer without it getting worse) and overall survival (the length of time that a patient is alive, with or without signs of cancer). |
|
| E.2.2 | Secondary objectives of the trial |
The additional study endpoints are outlined below:
I. Toxicity (adverse events).
II. Adherence to maintenance therapy - compliance with the regimen and dose reductions and interruptions. Maintenance therapy in ICON9 is given to a patient to prolong the time between chemotherapy treatments.
III. Progression free survival (PFS) and overall survival (OS) measured from the start of second-line chemotherapy. Second line chemotherapy is the chemotherapy given when initial treatment (first-line chemotherapy) doesn’t work, or stops working.
IV. Time from randomisation to the second subsequent treatment (TSST) or death.
V. Quality of life using EORTC QLQ C30 and OV28 questionnaires.
VI. Cost effectiveness using EQ-5D-5L questionnaires for economic evaluation.
VII. Progression free survival by CA125 (blood test measuring the CA125 tumour marker).
VIII. Treatment response rate (by CT scan or blood test) at 16 weeks of maintenance treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Histologically proven diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after day 1 of the last cycle of first-line platinum-based chemotherapy and requiring treatment with second-line platinum-based chemotherapy. Patients may be included post-surgery for relapsed disease if undertaken more than 6 months after progression from first-line therapy.
2. 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.
3. 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).
4. Completed a minimum of 4 cycles (and maximum of 6 cycles) of platinum-based chemotherapy for first relapse (2nd line treatment) with at least a partial response on imaging (CT or MRI) by RECIST 1.1 if measureable disease, or CA125 response by GCIG criteria if non-measurable disease. No CT/MRI or CA125 evidence of progression after surgical debulking and chemotherapy (above).
5. Prior front-line maintenance therapy with bevacizumab is permitted.
6. ECOG performance status 0-1.
7. Adequate bone marrow function, liver and renal function.
8. Availability of archival diagnostic tumour sample or tumour samples at relapse if patient has undergone further biopsy or surgical debulking.
9. Adequately controlled blood pressure (systolic blood pressure [SBP] ≤140 mmHg; diastolic blood pressure [DBP] ≤ 90mmHg) on maximum of 3 antihypertensive medications. |
|
| E.4 | Principal exclusion criteria |
1. Non-epithelial ovarian cancer, carcinosarcoma and mucinous carcinomas, ovarian clear-cell carcinoma.
2. Cerebrovascular accident (including transient ischemic attacks) within last 12 months.
3. Gastrointestinal impairment that could affect ability to take, or absorb oral medicines including sub-acute or complete bowel obstruction.
4. Symptomatic or clinically significant inflammatory bowel disease (Crohn’s disease or ulcerative colitis.
5. Evidence of severe or uncontrolled cardiac disease.
6. Evidence of active bleeding or bleeding diathesis.
7. Previous treatment with VEGFR tyrosine kinase inhibitors or PARP inhibitors are not permitted. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary outcome measures are:
I. 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)
II. Overall survival measured from the date of randomisation to the date of death from any cause
Both measured from the date of randomisation. These will be examined primarily in (a) all patients and (b) BRCA wild-type patients; then also in BRCA mutated positive (somatic/germline).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Progression free survival (RECIST 1.1) will be measured from randomisation to progression and overall survival (death from any cause) will be measured from randomisation to date of death. |
|
| E.5.2 | Secondary end point(s) |
I. Toxicity
II. PFS in BRCA mutated positive (somatic/germline) and BRCA wild-type subgroups.
III. Adherence with maintenance therapy - compliance and dose reductions and interruptions.
IV. PFS and OS measured from the start of second-line chemotherapy.
V. TSST (the time from randomisation to the second subsequent treatment or death).
VI. Quality of life (EORTC QLQ C30 and OV28, EQ-5D-5L (health economic analysis)).
VII. Progression free survival by CA125 – GCIG criteria.
VIII. Response rate (RECIST v1.1/CA125) at 16 weeks of treatment in patients who had RECIST v1.1 measurable disease or elevated CA125 at randomisation.
IX. Translational studies to identify predictors of response and prognostic markers.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
I. During treatment and follow up
II. From randomisation to disease progression or death
III. During treatment
IV. From start of second-line chemotherapy to disease progression or death
V. From randomisation to the second subsequent treatment or death
VI. Baseline, during treatment, at progression and on start on third-line chemotherapy
VII. From randomisation to disease progression by CA125 – GCIG criteria, or death
VIII. At 16 weeks of treatment
IX. At diagnosis, baseline, during treatment and at progression
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Belgium |
| Canada |
| Italy |
| Netherlands |
| New Zealand |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| For regulatory purposes the end of the trial will be after data on overall survival are sufficiently mature (e.g. up to 12 months after reaching the target number of events, or other time when recommended by the IDMC), at which point the ‘declaration of end of trial’ form will be submitted to participating regulatory authorities and Ethical Committees, as required. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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