Condition category
Cancer
Date applied
27/11/2017
Date assigned
19/01/2018
Last edited
05/09/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Karen Scott

ORCID ID

Contact details

Cancer Research UK Liverpool Cancer Trials Unit
C Block
Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Additional identifiers

EudraCT number

2016-004215-13

ClinicalTrials.gov number

Protocol/serial number

33260

Study information

Scientific title

Randomised phase II trial of Cediranib and Olaparib Maintenance in advanced/recurrent Cervical Cancer (COMICE)

Acronym

COMICE

Study hypothesis

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

North West – Greater Manchester South, 29/12/2017, ref: 17/NW/0634

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Gynaecological Cancers; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs

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

Phase

Phase II

Drug names

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 trial start date

21/12/2016

Overall trial end date

01/06/2020

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 108; UK Sample Size: 108

Participant 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

Recruitment start date

01/03/2018

Recruitment end date

01/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Liverpool Cancer Trials Unit
C Block, Waterhouse Building 3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Sponsor information

Organisation

The Clatterbridge Cancer Centre NHS Foundation Trust

Sponsor details

Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

AstraZeneca UK Limited

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal anticipated 2020.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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