Cervical cancer Cancer Malignant neoplasm of cervix uteri
Conditions
Interventions
The control arm (Arm A) is carboplatin AUC 5 and paclitaxel 175 mg/m^2 infused intravenously over 3 hours, repeated every 3 weeks for a maximum of 6 cycles, plus 20 mg placebo orally once daily.
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow (UK)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female and over 18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 3. Histologically proven carcinoma of the cervix (squamous, adenocarcinoma, adenosquamous mixed or small cell) 4. Either: 4.1. Persistent or relapsed inoperable disease after radical radiotherapy within the irradiated pelvis OR 4.2. Relapse after radical hysterectomy (after radical radiotherapy to pelvis if appropriate) OR 4.3. Extra pelvic metastases OR 4.4. Stage IVb disease at diagnosis 5. Patient not suitable for potentially curative surgical procedure 6. Measurable disease in at least one marker site 7. Adequate haematological function, as follows: 7.1. Haemoglobin greater than or equal to 10 g/dl 7.2. Neutrophils greater than or equal to 1.5 x 10^9/l 7.3. Platelets greater than or equal to 100 x 10^9/l 7.4. Calculated creatinine clearance greater than or equal to 35 ml/min (measured by EDTA) 8. Adequate biochemical function, as follows: 8.1. Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) 8.2. Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) less than or equal to 2.5 x ULN (or less than or equal to 5 x ULN if hepatic metastases) 9. Adequate coagulation as follows: 9.1.1. Prothrombin time ratio (PTR)/international normalised ratio (INR) less than or equal to 1.5 OR 9.1.2. PTR/INR between 2.0 and 3.0 for patients on stable doses of anticoagulants 9.2. Partial thromboplastin time less than 1.2 x control 10. Life expectancy greater than 12 weeks
Exclusion criteria
Exclusion criteria: 1. They have received prior chemotherapy, except cisplatin administered along with radiotherapy as primary treatment 2. Relapse is confined to the pelvis after radical surgery in circumstance where radiotherapy or chemoradiotherapy would be appropriate 3. Relapse is potentially treatable with exenterative surgery 4. History of nervous or psychiatric disorder that would prevent informed consent and compliance 5. History of prior malignancy within the previous 5 years except for successfully treated basal cell skin cancer or in-situ breast cancer 6. Pregnant or lactating women 7. 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 8. Evidence of uncontrolled infection 9. Tumour involvement of bowel wall 10. History of pelvic fistulae 11. Sub-acute or acute intestinal obstruction 12. Major surgery within 28 days or anticipated while on study 13. Significant traumatic injury during 4 weeks preceding the potential first dose of cediranib 14. Non-healing wound, ulcer or bone fracture 15. Active bleeding 16. History or evidence of thrombotic or haemorrhagic disorders 17. History of inflammatory bowel disease 18. Proteinuria greater than 1+ on dipstick on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein is less than 1.5 g in a 24-hour period 19. Significant cardiovascular disease (arterial thrombotic event within 12 months, uncontrolled hypertension or angina within 6 months, New York Heart Association (NYHA) grade 2 congestive cardiac failure, grade greater than or equal to 3 peripheral vascular disease or cardiac arrhythmia requiring medication). Patients with rate-controlled atrial fibrillation are eligible. 20. Prolonged QTc (corrected) interval of greater than 470 ms on electrocardiogram (ECG) or a family history of long QT syndrome 21. Central nervous system (CNS) disease (brain metastases, uncontrolled seizures or cerebrovascular accident/transient ischaemic attack/subarachnoid haemorrhage within 6 months) 22. History or clinical suspicion of spinal cord compression 23. Pre-existing sensory or motor neuropathy greater than or equal to grade 2 24. Known hypersensitivity to carboplatin or paclitaxel 25. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival Prior to progression patients will be followed up 2 monthly until end of year 2, every 6 months during years 3, 4 and 5 and yearly thereafter. After disease progression is documented, patients should be followed up 6 monthly during the first 5 years after randomisation and yearly thereafter. All primary and secondary outcomes will be assessed at all follow up visits until progression confirmed, after progression confirmed only applicable for overall survival to be assessed. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival 2. Response rate 3. Toxicity 4. Quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires modules C30 and CX26 Prior to progression patients will be followed up 2 monthly until end of year 2, every 6 months during years 3, 4 and 5 and yearly thereafter. After disease progression is documented, patients should be followed up 6 monthly during the first 5 years after randomisation and yearly thereafter. All primary and secondary outcomes will be assessed at all follow up visits until progression confirmed, after progression confirmed only applicable for overall survival to be assessed. | — |
Countries
England, United Kingdom
Outcome results
None listed