Does cediranib together with paclitaxel chemotherapy, or cediranib and olaparib, treat advanced endometrial cancer better than paclitaxel chemotherapy?
| ISRCTN | ISRCTN16320634 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16320634 |
| EudraCT/CTIS number | 2016-004617-28 |
| IRAS number | 216069 |
| Secondary identifying numbers | IRAS 216069 |
- Submission date
- 16/06/2017
- Registration date
- 18/08/2017
- Last edited
- 09/06/2023
- 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
Contact information
Dr Clare Freestone
Public
Public
Centre for Trials Research
College of Biomedical & Life Sciences
Cardiff University
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
| Phone | +44(0)29 20687095 |
|---|---|
| COPELIA@cardiff.ac.uk |
Dr Clare Freestone
Scientific
Scientific
Centre for Trials Research
College of Biomedical & Life Sciences
Cardiff University
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
| Phone | +44(0)29 20687095 |
|---|---|
| COPELIA@cardiff.ac.uk |
Study information
| Study design | Randomised controlled three-arm open-label parallel group multi-arm-multi-stage interventional trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | A 3-Arm Randomised Phase II Evaluation of Cediranib in Combination with Weekly Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy as Second-Line Therapy for Advanced/ Metastatic Endometrial Carcinoma or for disease relapse within 12 months of adjuvant carboplatin-paclitaxel chemotherapy |
| Study acronym | COPELIA |
| Study hypothesis | The aim of this study is to evaluate the therapeutic benefit of two novel combination regimens: cediranib and weekly paclitaxel (Arm 2) and cediranib-olaparib (Arm 3) compared to a widely-accepted standard treatment of weekly paclitaxel (Arm 1) for measurable, recurrent endometrial cancer where disease recurrence or progression has occurred after first-line platinum-based chemotherapy. |
| Ethics approval(s) | Approved 30/11/2017, South Central - Oxford B Research Ethics Committee (Whitefriars, Level 3, Block B, Lewin’s Mead, Bristol, BS1 2NT, UK; Tel: +44 (0)207 104 8241; Email: nrescommittee.southcentral-oxfordb@nhs.net), REC ref: 17/SC/0536 |
| Condition | Advanced/metastatic endometrial cancer |
| Intervention | Participants are randomised into one of the three study arms to receive treatment. Arm 1 (control): Paclitaxel will be administered at 80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle for 6 cycles. This is standard treatment and is the control arm. Arm 2: Paclitaxel at 80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle for 6 cycles with cediranib 20 mg orally once daily continuously in 28 day cycles until disease progression. Arm 3: Cediranib 20 mg orally once daily and Olaparib tablets 300 mg orally twice daily continuously in 28 day cycles until disease progression. Participants in all study arms are followed up after three and six months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 1. Paclitaxel 2. Cediranib 3. Olaparib |
| Primary outcome measure | Proportion of participants who are disease progression free at three months as determined by CT scan (RECIST v1.1 reporting) at three months. |
| Secondary outcome measures | 1. Radiological response rate during the trial assessed by CT scan (RECIST v1.1 reporting) 2. Median time until disease progression 3. Proportion of participants who are disease progression free at six months as determined by CT scan (RECIST v1.1 reporting) at six months 4. The median overall survival time, calculated as median time from participant enrolment to death with those still alive censored at date last seen 5. All toxicities associated with each treatment regimen as assessed by CTCAE version 4.03 monthly until disease progression, and at the end of treatment 6. Quality of life as measured by the EORTC QLQ-C30 and EN28 questionnaires at the start of the trial, monthly until disease progression, and at the end of treatment |
| Overall study start date | 01/10/2016 |
| Overall study end date | 31/12/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 129 |
| Participant inclusion criteria | 1. Histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma 2. Aged >16 years 3. One prior line of platinum-containing chemotherapy for advanced/ recurrent disease or relapse within 12 months of adjuvant platinum-based chemotherapy 4. Ability to provide written informed consent that includes genetic research on tissue derived from biopsies and biomarker research. (If a participant declines to participate in optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the participant. The participant will not be excluded from other aspects of the study). 5. Willing and able to comply with the trial visits and undergo treatment as scheduled 6. ECOG Performance Status 0-2 7. Life expectancy greater than 16 weeks 8. Measurable disease by RECIST v1.1 including at least one not previously irradiated lesion that is ≥ 10 mm in the longest diameter (lymph nodes must have short axis ≥ 15 mm) as determined by CT 9. Adequate haematological function: Hb ≥ 100.0 g/l with no requirement for blood transfusion in the last 28 days, neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l; coagulation: INR <1.4 (unless therapeutically anti-coagulated) and APPT ratio <1.4 10. Adequate liver function: bilirubin ≤1.5 x ULN, transaminases (ALT and AST ≤2.5x ULN. AST or ALT <5x ULN allowed in the presence of parenchymal liver metastases 11. Adequate renal function defined as calculated creatinine clearance using modified Wright or Cockcroft-Gault formula ≥ 51 ml/min or measured radioisotopic GFR ≥ 51ml/min 12. Urine protein:creatinine ratio (UPC) ≤1 OR ≤2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have UPC <0.5 on 2 consecutive samples 13. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction 14. Ability to swallow oral medication (tablets) 15. Willing to stop taking herbal supplements, and (if allocated to Arm 3) willing to not consume grapefruit or grapefruit juice, during the treatment period and for 30 days after end of trial treatment |
| Participant exclusion criteria | 1. Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required 2. Known positivity for hepatitis B, hepatitis C or HIV due to the risk of transmitting the infection through blood or other body fluids. 3. Resting ECG with QTc > 470 ms on 2 or more time points within a 24 hour period or family history of long QT syndrome 4. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is two weeks 5. Concomitant use of known strong (eg.phenobarbital,enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. 6. Pregnant or lactating. Pregnancy status in women of child bearing potential will be confirmed via a serum or urine pregnancy test no more than one week prior to randomisation, monthly during the treatment period, and at the end of treatment assessment. 7. Of child bearing potential AND not willing to ensure they use effective contraception throughout the treatment period and for six months following the end of treatment. Acceptable methods of contraception are: 7.1. True sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) 7.2. A combination of male condom plus one of the following: 7.2.1. Vasectomised sexual partner, with participant assurance that partner received post-vasectomy confirmation of azoospermia 7.2.2. Tubal occlusion 7.2.3. Intrauterine device provided coils are copper-banded 7.2.4. Etonogestrel implants (eg, Implanon®, Norplant®) 7.2.5. Normal and low dose combined oral pills 7.2.6. Hormonal shot or injection (eg, Depo-Provera) 7.2.7. Intrauterine system device (eg, levonorgestrel-releasing intrauterine system -Mirena®) 7.2.8. Norelgestromin/ethinyl estradiol transdermal system 7.2.9. Intravaginal device (eg, ethinyl estradiol and etonogestrel) 7.2.10. Cerazette (desogestrel). Cerazette is currently the only highly efficacious progesterone based pill. 8. Side effects of previous treatments have not resolved to grade 1 or less, with the exception of alopecia that is considered related to cytotoxic chemotherapy 9. Radiotherapy, chemotherapy, surgery or tumour embolisation within 28 days before the first dose of IMP 10. Additional concurrent anti-cancer therapy 11. Causes of malabsorption, e.g. uncontrolled diarrhoea or poorly controlled stoma 12. Bowel obstruction, fistulae, or extensive rectosigmoid involvement by cancer 13. Inadequately controlled hypertension, defined as ≥150/90 mmHg 14. Prior or concurrent therapy with a PARP or VEGF inhibitor 15. Known hypersensitivity to olaparib, cediranib or paclitaxel or any of the excipients of the products 16. Exposure to an investigational agent within 30 days or 5 half-lives (whichever is the longer) prior to enrolment 17. Considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent 18. Myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) or other clonal blood disorder, or features suggestive of MDS/AML 19. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years 20. Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation |
| Recruitment start date | 12/02/2018 |
| Recruitment end date | 31/12/2021 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
University College London Hospital
235 Euston Road
Fitzrovia
London
NW1 2BU
United Kingdom
Fitzrovia
London
NW1 2BU
United Kingdom
Mount Vernon Cancer Centre
Mount Vernon Hospital
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom
Velindre Cancer Centre
Velindre University NHS Trust
Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom
Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom
Bristol Haematology & Oncology Centre
Clinical Trials Unit
Bristol Haematology & Oncology Centre
University Hospitals Bristol NHS Foundation Trust
Horfield Road
Bristol
BS2 8ED
United Kingdom
Bristol Haematology & Oncology Centre
University Hospitals Bristol NHS Foundation Trust
Horfield Road
Bristol
BS2 8ED
United Kingdom
Churchill Hospital
c/o Dr Rene Roux
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
The Royal Marsden Hospital (Surrey)
c/o Dr Susana Banerjee
Downs Road
Sutton
SM2 5PT
United Kingdom
Downs Road
Sutton
SM2 5PT
United Kingdom
The Royal Marsden Hospital
c/o Dr Susana Banerjee
Fulham Road
Chelsea
London
SW3 6JJ
United Kingdom
Fulham Road
Chelsea
London
SW3 6JJ
United Kingdom
Beatson West of Scotland Oncology Centre
c/o Dr Azmat Sadoyze
Gartnavel General Hospital
1089 Great Western Road
Glasgow
G12 0YN
United Kingdom
Gartnavel General Hospital
1089 Great Western Road
Glasgow
G12 0YN
United Kingdom
Northern Centre for Cancer Care
c/o Dr Yvette Drew
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom
Guildford
GU2 7XX
United Kingdom
Leicester Royal Infirmary
c/o Dr Joey Wood
Hope Clinical Trials Facility
Level 2 Osborne Building
Leicester
LE1 5WW
United Kingdom
Hope Clinical Trials Facility
Level 2 Osborne Building
Leicester
LE1 5WW
United Kingdom
Clatterbridge Cancer Centre
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Bebington
Wirral
CH63 4JY
United Kingdom
Guys and St Thomas NHS Trust
c/o Dr Rebecca Kristeleit
OHCT
1st floor Chapel Wing
Guy's Hospital
London
SE1 9RY
United Kingdom
OHCT
1st floor Chapel Wing
Guy's Hospital
London
SE1 9RY
United Kingdom
Airedale NHS Foundation Trust
c/o Dr Clara Sentamans
Skipton Road
Steeton
Bradford
BD20 6TD
United Kingdom
Skipton Road
Steeton
Bradford
BD20 6TD
United Kingdom
Sponsor information
University of Manchester
University/education
University/education
The University of Manchester
Oxford Rd
Manchester
M13 9PL
England
United Kingdom
"ROR" |
https://ror.org/027m9bs27 |
|---|
Funders
Funder type
Industry
AstraZeneca
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | All presentations and publications relating to the trial will be authorised by the TMG and Sponsor. The main trial results will be published in the name of the trial in a peer-reviewed journal, on behalf of all collaborators. The manuscript will be prepared by a writing group, appointed from amongst the Trial Management Group, and this may also include high accruing clinicians and/or other people who contribute to the trial. All participating centres and clinicians will be acknowledged in this main publication together with appropriate staff from the CTR. Authorship of any secondary publications, e.g. relating to the various biological studies, will reflect the intellectual and scientific input of individuals into these studies, and will not necessarily be the same as on the primary publication. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request upon consideration by the TMG. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
09/06/2023: The intention to publish date was updated from 30/06/2023 to 30/12/2023.
09/07/2021: The trial participating centres "Guys and St Thomas NHS Trust" and "Airedale NHS Foundation Trust" have been added.
27/05/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/05/2021 to 31/12/2021.
2. The overall end date was changed from 01/06/2022 to 31/12/2022.
3. The intention to publish date was changed from 01/06/2022 to 30/06/2023.
02/09/2020: Recruitment to this study is no longer paused.
24/04/2020: Due to current public health guidance, recruitment for this study has been paused.
17/12/2019: Clatterbridge Cancer Centre has been added to the trial participating centres.
18/11/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/10/2019 to 01/05/2021.
2. The overall trial end date was changed from 01/04/2020 to 01/06/2022.
3. The intention to publish date was changed from 30/04/2021 to 01/06/2022.
10/07/2019: The trial participating centres were updated and the ethics approval details were added.
01/07/2019: The trial participating centres were updated.
15/04/2019: Beatson West of Scotland Oncology Centre and the Northern Centre for Cancer Care have been added to the trial participating centres.
28/03/2019: The following changes have been made to the trial record:
1. Churchill Hospital, the Royal Marsden Hospital and the Royal Marsden Hospital (Surrey) have been added as trial participating centres.
2. The trial contacts have been updated.
21/01/2019: Velindre Cancer Centre and Bristol Haematology & Oncology Centre have been added as trial participating centres.
19/10/2018: Mount Vernon Cancer Centre has been added as a trial participating centre.
08/10/2018: The following changes have been made to the trial record:
1. The Christie NHS Foundation Trust and University College London Hospital have been added as trial participating centres
2. Centre for Trials Research (Cardiff) was removed as a trial participating centre
2. Cancer Research UK was removed as a funder
19/06/2018: Cancer Research UK lay summary link added to plain English summary field.
07/06/2018; Internal review
14/05/2018: Internal review.
16/01/2018: Internal review.
15/01/2018: The recruitment start date was changed from 01/07/2017 to 12/02/2018.
16/10/2017: Internal review.
