E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
epitehlial ovarian carcinoma, fallopian tube carcinoma, primary serous peritoneal carcinoma relapsing more than 6 months after completion of first-line platinum based chemotherapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033131 |
E.1.2 | Term | Ovarian carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
to assess the safety and efficacy of AZD2171 in combination with platinum-based chemotherapy and as a single agent maintenance therapy, in women with ovarian cancer relapsing more than 6 months following completion of first line platinum based treatment.
The main outcome measure is Progression Free Survival (PFS) |
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E.2.2 | Secondary objectives of the trial |
to assess overall survival, toxicity and quality of life (QoL) being secondary outcome measures
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translational Research (biomarkers and pharmacogenomics), this is part of the main trial protocol (same date and version). The objectives are to assess whether it is possible to identify biomarkers that identify the patients who will most benefit from AZD2171 so that toxicity and costs can be minimised; and to assess whether it is possible to identify markers of early clinical progression during protocol defined treatment, so that ineffective therapy can be stopped and alternatives prescribed. |
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E.3 | Principal inclusion criteria |
1. Females aged 18 years with previous histologically proven diagnosis of
• Epithelial ovarian carcinoma
• Fallopian tube carcinoma
• Primary serous peritoneal carcinoma
requiring treatment with further platinum-based chemotherapy > 6 months after their last cycle of first-line chemotherapy and 6 weeks after maintenance that is not chemotherapy based .
2. Signed informed consent and ability to comply with the protocol
3. Ability to commence treatment within approximately 2 weeks of randomisation
4. CT or MRI proven relapsed disease (measurable or non-measureable)d
5. ECOG performance status 0-1e
6. Life expectancy more than 12 weeks
7. If there is a past history of a solid tumour (other than ovarian cancer), this must have been treated curatively more than five years ago with no evidence of recurrence, with the exception of patients who have synchronous endometrial cancer (Stage I G1,G2) with their ovarian cancer
8. If prior anthracycline or chest radiotherapy, Left Ventricular Ejection Fraction (LVEF) > institutional lower limit of normal
9. Adequate bone marrow function
• Absolute Neutrophil Count (ANC) 1.5 x 109/l
• Platelets (Plt) 100 x 109/l
• Haemoglobin (Hb) 9g/dl (can be post transfusion)
10. Adequate liver function (within 14 days before randomisation)
• Serum bilirubin (BR) ≤ 1.5 x ULN
Serum transaminases ≤ 2.5 x ULNf
11. Adequate renal function
• Serum creatinine ≤ 1.5 ULN and calculated creatinine clearance >50 ml/min
• Urine dipstick for proteinuria <2+. If urine dipstick is > 2+ on two occasions more than one week apart then a 24 hour urine must demonstrate < 1 g of protein in 24 hours or protein/creatinine ratio < 1.5.
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E.4 | Principal exclusion criteria |
1. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum
2. Poorly controlled hypertension (persistently elevated > 150/100mmHg, either systolic or diastolic or both, despite anti-hypertensive medication)
3. History of inflammatory bowel disease (Crohn’s Disease or Ulcerative Colitis)
4. Malignancies other than ovarian cancer within 5 years prior to randomisation, except for synchronous endometrial cancer (Stage I G1,G2) with ovarian cancer, adequately treated carcinoma in situ of the cervix and/or basal cell skin cancer. Patients who have a past history of a solid tumour, treated curatively, more than five years prior to randomisation, with no evidence of recurrence, are still eligible to enter ICON6
5. Previous radiotherapy within approximately 21 days prior to anticipated start of treatment
6. Treatment with any other investigational agent within 6 weeks prior to entering this trial. Patients are still eligible for entry into ICON6 if they have received previous treatment for ovarian cancer with either bevacizumab, erlotinib, or a Cox-2 inhibitor as long as more than 6 weeks have elapsed since the last treatment
7. Arterial thrombotic event (including transient ischaemic attack [TIA], cerebrovascular accident [CVA] and peripheral arterial embolus) within the previous 12 months.
8. GI impairment that could affect ability to take, or adsorption of, oral medicines including sub acute or complete bowel obstruction
9. Known hypersensitivity to cediranib or other VEGF inhibitors
10. Major surgery within 2 weeks before anticipated start of treatment
11. Significant haemorrhage of > 30ml in a single episode within 3 months or any haemoptysis
12. Evidence of severe or uncontrolled cardiac disease
• Myocardial infarct [MI] or unstable angina within 12 months
• New York Health Association (NYHAg) ≥ grade 2 congestive heart failure (CHF)
• Cardiac ventricular arrhythmias requiring medication.
• History of 2nd or 3rd degree atrioventricular conduction defects.
13. Prolonged QTc (corrected) interval of > 470msec on ECG, or a family history of long QT syndrome.
14. Persisting ≥ Grade 2 CTC toxicity (except alopecia and neuropathy) from previous anti-cancer treatment. If peripheral sensory or motor neuropathy ≥ grade 2 then paclitaxel can be omitted from the chemotherapy at the discretion of the treating physician
15. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory in the case of suspected brain metastases. Spinal MRI is mandatory in the case of suspected spinal cord compression. Patients with unstable, untreated brain or meningeal metastases are not eligible.
16. Inability to attend or comply with treatment or follow-up scheduling
17. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
18. Fertile women of childbearing potential not willing to use adequate contraception for the duration of trial treatment and at least 6 months after
19. Any other severe uncontrolled medical condition or disease
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E.5 End points |
E.5.1 | Primary end point(s) |
Stage 1: safety
Stage 2: progression free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The second stage will be analysed when approximately 176 events have been observed in arms A and C |
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E.5.2 | Secondary end point(s) |
Overall Survival (OS)
Toxicity
Quality of Life (QoL)
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
quality of life, translational research |
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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) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 55 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | Information not present in EudraCT |
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 |
Canada |
New Zealand |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The trial will be considered closed when all patients have discontinued trial drug, and a sufficient number of deaths have been observed to ascertain whether there is an overall surival benefit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
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 | 0 |