COMICE: A Randomised Double Blind Placebo Controlled Phase II Clinical Trial of Cediranib and Olaparib Maintenance in Advanced/Recurrent Cervical Cancer
| ISRCTN | ISRCTN10841582 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10841582 |
| EudraCT/CTIS number | 2016-004215-13 |
| IRAS number | 209375 |
| Secondary identifying numbers | CPMS 33260, IRAS 209375 |
- Submission date
- 27/11/2017
- Registration date
- 19/01/2018
- Last edited
- 29/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Mrs Diane Carlton
Scientific
Scientific
Cancer Research UK Liverpool Cancer Trials Unit
C Block, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 151 795 7323 |
|---|---|
| dcarlton@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Randomised phase II trial of Cediranib and Olaparib Maintenance in advanced/recurrent Cervical Cancer (COMICE) |
| Study acronym | COMICE |
| Study objectives | The primary purpose of this study is to compare median survival of patients with metastatic or recurrent cervical cancer when treated with Cediranib (antiangiogenic agent) and Olaparib (PARP inhibitor) compared with a placebo after having platinum based chemoradiotherapy. Secondary to this is to examine drug toxicity and tolerability to the combination of drugs. |
| Ethics approval(s) |
Approved 29/12/2017, North West Greater Manchester South Research Ethics Committee; ), ref: (3rd Floor, Barlow House 4 Minshull Street, Manchester, M1 3DZ, United Kingdom; +44 (0)207 1048014; gmsouth.rec@hra.nhs.uk), ref: 17/NW/0634 |
| Health condition(s) or problem(s) studied | Cervical cancer |
| Intervention | Participants are randomly allocated to one of two study arms: ARM 1: Cediranib 20mg OD + Olaparib 300mg BD ARM 2: Placebo Cediranib + Placebo Olaparib Participants are treated until progression of disease, unacceptable toxicity or withdrawal of consent. Participation in the study continues until there is a withdrawal of consent or death. Participants who stop treatment before having developed progressive disease (PD) are assessed every 8 weeks for response until PD occurs. The study ends when the last participant recruited has completed a minimum of seven month follow up. The anticipated recruitment period is 14 months therefore the maximum duration of a patient on this study will be 21 months. After study end participants still deemed to be benefitting from study medication are allowed to continue off study with discretionary use of the drugs until disease progression. |
| Intervention type | Other |
| Primary outcome measure | Progression Free Survival is measured from date of randomisation until the earlier of date of progression or death, progression measured using RECIST 1.1 from results of CT/MRI scans scheduled every 8 weeks (additional scans may be performed between scheduled visits if it is believed that the patient has progressive disease), and compared to results obtained prior to starting study treatment. |
| Secondary outcome measures | 1. Overall Survival Overall survival is measured from date of randomisation to date of death 2. Best Objective Response Is measured as the highest value of response observed using RECIST 1.1 comparing results from 8-weekly scheduled MRI/CT scans to results obtained prior to starting study treatment 3. Quality of Life Is measured using results from FACT-Cx questionnaire completed at 4-weekly intervals until the earlier of disease progression or 28 weeks treatment 4. Toxicity Is measured using AE data (described using CTCAE v4.03) collected at 4-weekly visits whilst on study treatment and from SAE data (described using CTCAE v4.03) collected whilst patient is on study |
| Overall study start date | 21/12/2016 |
| Completion date | 30/06/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 108; UK Sample Size: 108 |
| Total final enrolment | 74 |
| Key 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: 8.1. Haemoglobin > 10g/dl (with no blood transfusion in the 28 days prior to randomisation) Neutrophils > 1.5 x 109/l 8.2. Platelets > 100 x 109/l 8.3. Bilirubin < 1.5 x ULN 8.4. ALT or AST/ SGOT < 3 x ULN (or ≤5 x ULN if hepatic metastases present) 8.5. Alkaline Phosphatase < 3 x ULN (or ≤5 x ULN if hepatic metastases present) 8.6. Adequate coagulation, as follows: 8.7. Prothrombin ratio (PTR) / INR ≤ 1.5 or 8.8. PTR / INR between 2.0 and 3.0 for patients on stable doses of anticoagulants 8.9. Partial thromboplastin time <1.2 x control 9. Life expectancy >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 |
| Key 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: 6.1. 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 6.2. 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 < 1.5g in a 24 hour period. 19. Significant cardiovascular disease (arterial thrombotic event within 12 months, uncontrolled hypertension, myocardial infarction or angina within 6 months, NYHA grade 2 or worse congestive cardiac failure, grade > = 3 peripheral vascular disease or cardiac arrhythmia requiring medication). Patients with rate-controlled atrial fibrillation are eligible 20. Prolonged QTc (corrected) interval of > 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 intervals and averaged. If the first two diastolic readings differ by more than 5mmHG, then an additional reading should be obtained and averaged) 23. History of significant gastrointestinal impairment. Defined as active inflammatory bowel disease, bowel obstruction or any condition judged by the investigator to adversely impact on drug absorption or within 3 months prior to starting treatment 24. Patients with myelodysplastic syndrome/acute myeloid leukaemia 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 26. Patients who have been treated with potent inhibitors of CYP3A4 and 2C8 such as amiodaraone, clarithromycin, erythromycin, simvastatin, atorvastatin, lovastatin, montelukast sodium, verapamil, ketoconazole, miconazole, indinovir (and other antivirals) and diltiazem within 2 weeks of the first planned dose of cediranib will be excluded [NB These drugs are also prohibited during trial period] 27. Patients treated with CYP3A inhibitorsWithin 2 weeks of the first planned dose for strong inhibitors, and at least 1 week for moderate inhibitors 28. Concomitant use of known strong CYP3A inducers 29. (LVEF) < lower limit of normal (LLN) per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines 30. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV, or who are receiving immunosuppressive treatment 31. History of intra-abdominal abscess within 3 months prior to starting treatment 32. Uncontrolled intercurrent illness 33. No prior allogeneic bone marrow transplant or double umbilical cord b |
| Date of first enrolment | 01/03/2018 |
| Date of final enrolment | 30/11/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cancer Research UK Liverpool Cancer Trials Unit
C Block, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Sponsor information
The Clatterbridge Cancer Centre NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
Clatterbridge Road
Bebington
Wirral
CH63 4JY
England
United Kingdom
"ROR" |
https://ror.org/05gcq4j10 |
|---|
Funders
Funder type
Industry
AstraZeneca UK Limited
No information available
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal anticipated 2020. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
29/01/2024: The following changes were made:
1. An IRAS number was added.
2. The total final enrolment was added.
3. The recruitment end date was changed from 01/11/2019 to 30/11/2022.
4. Full REC contact information was added.
14/11/2022: The following changes were made to the trial record:
1. The overall end date was changed from 01/11/2022 to 30/06/2023.
2. The intention to publish date was changed from 01/08/2023 to 31/12/2023.
09/06/2021: The following changes were made to the trial record:
1. The contact was changed.
2. The overall end date was changed from 01/06/2020 to 01/11/2022.
3. The intention to publish date was changed from 31/12/2020 to 01/08/2023.
08/06/2021: The contact email was changed.
22/12/2020: Internal review.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Gynaecological Cancers; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs" to "Cervical cancer" following a request from the NIHR.
05/03/2019: Cancer Research UK lay summary link added to plain English summary field.
05/09/2018: The recruitment end date was changed from 01/05/2019 to 01/11/2019.
06/06/2018: Internal review
14/05/2018: Internal review
