Randomised Phase II Trial of Cediranib and Olaparib Maintenance in Advanced/Recurrent Cervical Cancer (COMICE)

INTERVENTION: Product Name: Cediranib Product Code: AZD2171 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Cediranib maleate (Cediranib) Current Sponsor code: AZD2171 Maleate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Olaparib Product Code: AZD2281 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Olaparib CAS Number: 763113‐22‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: 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: 20.0 Level: LLT Classification code 10008236 Term: Cervical cancer stage IV System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: ; 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.; Primary end point(s): Primary Outcome Measure ‐ Progression Free Survival. 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. 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 OUTCOME: ; 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.; ; 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 < 1.5 x U