E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic/ Recurrent carinoma of cervix |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041848 |
E.1.2 | Term | Squamous cell carcinoma of the cervix |
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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008224 |
E.1.2 | Term | Cervical adenocarcinoma |
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 |
The aim of the study is to provide preliminary evidence regarding whether the addition of cediranib to a combination of carboplatin and paclitaxel will increase progression free survival by 50% in patients with metastatic recurrent cervical cancer. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to provide estimates of differences in response, survival, toxicity, quality of life and pharmacodynamic end-points between the study arms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female and over 18 years of age. • ECOG performance status 0, or 1. • Written Informed Consent • Histologically proven carcinoma of the cervix (squamous, adenocarcinoma or adenosquamous mixed ). • Either: 1. Persistent or relapsed inoperable disease after radical radiotherapy within the irradiated pelvis or 2. Relapse after radical hysterectomy (after radical radiotherapy to pelvis if appropriate) or 3. Extra pelvic metastases or 4. Stage IVb disease at diagnosis • Patient not suitable for potentially curative surgical procedure. • Measurable disease in at least one marker site. • Adequate haematological function, as follows: Haemoglobin > 10g/dl Neutrophils > 1.5 x 109/l Platelets > 100 x 109/l Calculated Creatinine Clearance > 35mls/min (measured by EDTA) • Adequate biochemical function, as follows: Bilirubin < 1.5 x ULN ALT or AST < 2.5 x ULN (or ≤5 x ULN if hepatic metastases present) Alkaline Phosphatase < 2.5 x ULN (or ≤5 x ULN if hepatic metastases) • Adequate coagulation, as follows: Prothrombin ratio (PTR) / INR ≤ 1.5 or PTR / INR between 2.0 and 3.0 for patients on stable doses of anticoagulants Partial thromboplastin time <1.2 x control • Life expectancy >12 weeks
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E.4 | Principal exclusion criteria |
• They have received prior chemotherapy, except cisplatin administered along with radiotherapy as primary treatment. • Relapse is confined to the pelvis after radical surgery in circumstance where radiotherapy or chemoradiotherapy would be appropriate. • Relapse is potentially treatable with exenterative surgery. • History of nervous or psychiatric disorder that would prevent informed consent and compliance • History of prior malignancy within the previous 5 years except for successfully treated basal cell skin cancer or in-situ breast cancer • Pregnant or lactating women. • Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least six months afterwards • Evidence of uncontrolled infection. • History of pelvic fistulae. • Sub-acute or acute intestinal obstruction. • Major surgery within 28 days or anticipated while on study. • Significant traumatic injury during 4 weeks preceding the potential first dose of cediranib. • Non-healing wound, ulcer or bone fracture. • Active bleeding. • History or evidence of thrombotic or haemorrhagic disorders. • History of inflammatory bowel disease. • Proteinuria > 1+ on dipstick on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein is <1.5g in a 24 hour period. • Significant cardiovascular disease (arterial thrombotic event within 12 months, uncontrolled hypertension or angina within 6 months, NYHA grade 2 congestive cardiac failure, grade ≥ 3 peripheral vascular disease or cardiac arrhythmia requiring medication). Patients with rate-controlled atrial fibrillation are eligible. • Prolonged QTc (corrected) interval of >470ms on ECG or a family history of long QT syndrome. • CNS disease (brain metastases, uncontrolled seizures or cerebrovascular accident/transient ischaemic attack /subarachnoid haemorrhage within 6 months). • History or clinical suspicion of spinal cord compression. • Pre-existing sensory or motor neuropathy ≥ grade 2. • Known hypersensitivity to carboplatin or paclitaxel • 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 • Any unresolved toxicity ≥ CTC Grade 2 from previous systemic anti-cancer therapy except haematological toxicity (see inclusion criteria “Adequate haematological function”) and alopecia. • A history of poorly controlled hypertension or resting BP>150/100 mmHG in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minutes intervals and averaged. If the first two diastolic readings differ by more than 5mmHG, then an additional reading should be obtained and averaged). • Requiring intravenous nutritional support. • History of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure of this study is progression free survival. |
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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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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For the purpose of Clinical Trial Authorisation the trial is deemed to have ended 30 days after the last patient remaining on treatment receives the last dose of Cediranib or Placebo.
For purposes of the main REC approval, the study end date is deemed to be the date of the last data capture. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |