Advanced recurrent and metastatic cervical cancer. MedDRA version: 20.0 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10008235 Term: Cervical cancer stage III System Organ Class: 100000004864 MedDRA version: 2
Conditions
Interventions
Product Name: Cediranib
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cediranib maleate (Cediranib)
Sponsors
The Clatterbridge Cancer Centre NHS Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients over 18 years of age 2. Histologically proven carcinoma of the cervix (squamous, adenocarcinoma or mixed adeno/squamous). 3. Completion of first line platinum-based chemotherapy for advanced /recurrent disease, leading to either a complete response, partial response or stable disease. 4. ECOG performance status 0 or 1 5. Randomisation within 6 weeks of completion of chemotherapy 6. Patients may have received previous chemoradiotherapy and neoadjuvant chemotherapy given with a curative intent. 7. Creatinine Clearance = 51mls/min 8. Adequate haematological and biochemical function, as follows: Haemoglobin > 10g/dl (with no blood transfusion in the 28 days prior to randomisation) Neutrophils > 1.5 x 109/l Platelets > 100 x 109/l Bilirubin 12 weeks. 10. Informed written consent 11. Contrast enhanced computerised tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis and a CT scan of the chest within 28 days prior to commencing randomisation (with RECIST 1.1) 12. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction 13. Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: 1. Disease that is potentially treatable with exenterative surgery. 2. Relapse confined to the pelvis after radical surgery in circumstance where radiotherapy or chemoradiotherapy would be appropriate. 3. More than one line of prior chemotherapy for advanced/recurrent disease. Neoadjuvant chemotherapy is not counted. 4. Prior treatment with anti-angiogenic agents (with the exception of bevacizumab given as part of first line chemotherapy) 5. Persisting =Grade 2 CTCAE from previous anti-cancer previous systemic anti-cancer therapy except haematological toxicity (see inclusion criteria “Adequate haematological function”) and alopecia. 6. History of other malignancy within the previous 5 years except for: Curatively treated basal cell or squamous cell carcinoma of skin; in situ cancer of the cervix, ductal carcinoma in situ of the breast or stage 1, grade 1 endometrial carcinoma. Curatively treated other solid tumors including lymphomas (without bone marrow involvement) with no evidence of disease for =5 years prior to start of IPs. 7. Pregnant or lactating women. 8. 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 9. Evidence of uncontrolled infection. (Defined as infection that cannot be resolved readily with antibiotics prior to patient entry into the trial for example a pelvic collection) 10. History of pelvic fistulae. 11. History of abdominal fistula that has been surgically corrected within 6 months of starting treatment. Patient should be deemed low risk of recurrent fistula 12. Sub-acute or acute intestinal obstruction. 13. Major surgery within 28 days or anticipated while on study. 14. Non-healing wound, ulcer or bone fracture. 15. Active bleeding. 16. History or evidence of thrombotic or haemorrhagic disorders. 17. History of stroke or transient ischemic attack within 6 months 18. Proteinuria > 1+ on dipstick on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein is 470ms on ECG or a family history of long QT syndrome. 21. Patients with symptomatic uncontrolled brain or meningeal metastases CNS disease (A scan to confirm the absence of brain metastases is not required) 22. A history of poorly controlled hypertension or resting BP>140/90 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 minute int
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate improved Progression Free Survival (PFS) compared to placebo for patients with advanced/recurrent cervical cancer after systemic chemotherapy for advanced /recurrent disease. ;Secondary Objective: The secondary objectives are to establish toxicity, tolerability and quality of life for patients receiving the combination of Cediranib/Olaparib compared to the placebo. ;Primary end point(s): Primary Outcome Measure - Progression Free Survival.;Timepoint(s) of evaluation of this end point: Patients will be seen on a 4 weekly basis during the time they are on active treatment and will be treated until disease progression. RECIST measurements will be taken every 8 weeks either by CT or MRI scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival Tumour Response (RECIST v 1.1) Quality of Life Safety (Toxicity, SAEs) ; Timepoint(s) of evaluation of this end point: Overall survival until trial end. Event of interest = death from any cause Event date = date of death Tumour response Patients will be seen on a 4 weekly basis during the time they are on active treatment and will be treated until disease progression. RECIST measurements will be taken every 8 weeks either by CT or MRI scan. Quality of life will be completed at the four weekly visits up to and only including the 28th week then stop. We will not collect QoL forms if DP is at >7 months Safety AE information will be collected until at least 28 days after the last dose of study therapy is administered or until all study therapy-related AEs have resolved, stabilised or been deemed irreversible. | — |
Countries
United Kingdom
Contacts
Public ContactKaren Scott
Liverpool Cancer Trials Unit
Outcome results
None listed