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CarcinosarcomaPhase 2COPELIANCT03570437

Does Cediranib With Paclitaxel, or Cediranib and Olaparib, Treat Advanced Endometrial Cancer Better Than Paclitaxel?

A Phase 2 study testing Paclitaxel, Cediranib and Olaparib in people with Carcinosarcoma and Endometrial Neoplasms, run by University of Manchester at 15 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The COPELIA trial is evaluating two new tablet medications in endometrial cancer for the first time. It will include 129 women aged 16 years or older with advanced endometrial cancer whose cancer has worsened after their initial chemotherapy treatment. Read more about this study

Who is it for?
Ages 16 years and older, women only
Conditions the study is for
Carcinosarcoma, Endometrial Neoplasms
What is being tested?
Paclitaxel, Cediranib and Olaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
15 sitesUnited Kingdom
Study dates
17 May 2018to 30 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma.
  • Aged >16 years.
  • All participants must have received at least one prior line of platinum-based chemotherapy (either in the adjuvant or recurrent disease setting). In addition, ONE of the following must apply:
  • have disease recurrence/ progression within 18 months of completing adjuvant chemotherapy and have received no cytotoxic chemotherapy for recurrent/ progressive endometrial cancer.
  • OR
  • have received one or two prior lines of cytotoxic chemotherapy for recurrent/ progressive endometrial cancer (not counting adjuvant treatment).
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  • Dose-dense weekly paclitaxel is an appropriate treatment option.
  • 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).
  • Willing and able to comply with the trial visits and undergo treatment as scheduled.
  • ECOG Performance Status 0-1.
  • Life expectancy greater than 16 weeks.
  • 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.
  • Adequate haematological function: Hb ≥ 90.0 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.
  • 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.
  • Adequate renal function defined as calculated creatinine clearance using modified Wright or Cockcroft-Gault formula ≥ 51 ml/min or measured radioisotopic GFR ≥ 51ml/min.
  • Negative or trace proteinuria reading on urine dipstick. Patients with 1+ proteinuria on dipstick must have ≤1+ proteinuria on consecutive dipstick taken no less than 1 week later. Patients with ≥2+ proteinuria on dipstick must have 24 hour urinary protein excretion ≤1 g.
  • Adequately controlled thyroid function, with no symptoms of thyroid dysfunction.
  • Ability to swallow oral medication (tablets).
  • 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.

Who cannot join

  • Prior treatment with dose-dense weekly paclitaxel.
  • Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required.
  • Known positivity for hepatitis B, hepatitis C or HIV due to the risk of transmitting the infection through blood or other body fluids and potential for reactivation during treatment.
  • Resting ECG with QTc > 470 ms on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • 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.
  • Concomitant use of known strong CYP3A inducers (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.
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  • Pregnant or lactating. Pregnancy status in women of child bearing potential will be confirmed via a serum or urine pregnancy test prior to randomisation, monthly during the treatment period, and at the end of treatment assessment.
  • 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:
  • true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) ii. a combination of male condom plus one of:
  • vasectomised sexual partner, with participant assurance that partner received post-vasectomy confirmation of azoospermia
  • Tubal occlusion
  • Intrauterine device provided coils are copper-banded
  • Etonogestrel implants (eg, Implanon®, Norplant®)
  • Normal and low dose combined oral pills
  • Hormonal shot or injection (eg, Depo-Provera)
  • Intrauterine system device (eg, levonorgestrel-releasing intrauterine system -Mirena®)
  • Norelgestromin/ethinyl estradiol transdermal system
  • Intravaginal device (eg, ethinyl estradiol and etonogestrel)
  • Cerazette (desogestrel). Cerazette is currently the only highly efficacious progesterone based pill.
  • 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.
  • Radiotherapy, chemotherapy, surgery or tumour embolisation within 28 days before the first dose of IMP.
  • Additional concurrent anti-cancer therapy.
  • Causes of malabsorption, e.g. uncontrolled diarrhoea or poorly controlled stoma.
  • Bowel obstruction, fistulae, impending fistulation seen on radiological imaging, or extensive rectosigmoid involvement by cancer.
  • Inadequately controlled hypertension, defined as ≥150/90 mmHg.
  • Prior or concurrent therapy with a PARP or VEGF inhibitor.
  • Known hypersensitivity to olaparib, cediranib or any of the excipients of the products.
  • Known hypersensitivity to paclitaxel that in the opinion of the investigator would prevent administration of a weekly paclitaxel regimen.
  • Exposure to an investigational agent within 30 days or 5 half-lives (whichever is the longer) prior to enrolment.
  • 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.
  • Myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) or features suggestive of MDS/AML.
  • 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.
  • Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United Kingdom15 sites

  • Royal United Hospitals Bath NHS Foundation Trust

    Bath, BA1 3NG

  • Bristol Haematology & Oncology Centre, University Hospitals Bristol NHS Foundation Trust

    Bristol, BS2 8ED

  • Velindre Cancer Centre, Velindre University NHS Trust

    Cardiff, CF14 2TL

  • Beatson West of Scotland Oncology Centre

    Glasgow, G12 0YN

  • Royal Surrey County Hospital

    Guildford, Surrey, GU2 7 XX

  • Airedale NHS Foundation Trust

    Keighley, BD20 6TD

  • Hope Clinical Trials Facility, Leicester Royal Infirmary

    Leicester, LE1 5WW

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool, L7 8YA

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2BU

  • Guys & St Thomas NHS Trust

    London, SE1 9RT

  • Royal Marsden Hospitals

    London

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Northern Centre for Cancer Care, Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

  • Mount Vernon Cancer Centre

    Northwood, Middlesex, HA6 2RN

  • The Churchill Hospital, Old Road, Headington

    Oxford, OX3 7LE

Other trials in United Kingdom

About this study

Official title: A 3-Arm Randomised Phase II Evaluation of Cediranib in Combination With Weekly Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy for Advanced Endometrial Carcinoma or for Disease Relapse Within 18 Months of Adjuvant Carboplatin-paclitaxel Chemotherapy.

The COPELIA trial is evaluating two new tablet medications in endometrial cancer for the first time. It will include 129 women aged 16 years or older with advanced endometrial cancer whose cancer has worsened after their initial chemotherapy treatment. Participants will be allocated at random to one of three groups:

  1. The first group (Arm 1) will receive a standard (routine) treatment for patients with endometrial cancer known as paclitaxel. This is a chemotherapy drug that is routinely used to treat patients with different cancers including ovarian, breast, lung and endometrial cancer. Paclitaxel works by stopping the growth of cancer cells.
  2. The second group (Arm 2) will receive the standard paclitaxel treatment once a week in addition to a new drug called cediranib. Cediranib is a tablet medication and works by blocking new blood vessel formation. Cediranib has been tested in women with endometrial cancer before but not alongside chemotherapy treatment.
  3. The third group (Arm 3) will receive two new tablet medications, cediranib and olaparib. Olaparib works by preventing cancer cells repairing DNA effectively. The use of olaparib and cediranib together has been shown to be effective in a common type of ovarian cancer but has not been evaluated as a treatment for endometrial cancer before.
Read more

The main objectives of the COPELIA trial are to work out:

  1. Whether the two new treatments, cediranib-paclitaxel (Arm 2) and cediranib-olaparib (Arm 3) are more effective at controlling endometrial cancer than standard paclitaxel chemotherapy (Arm 1)
  2. Whether the two new treatments cause more or fewer side-effects than standard chemotherapy
  3. How each of these treatments impact on the daily life of women receiving the treatment by asking trial participants to regularly complete quality of life questionnaires
  4. Whether we can learn how these treatments work in women with endometrial cancer by taking some additional blood tests for research.
Read the detailed description

COPELIA is a phase II, randomised, three-arm open-label trial which will recruit 129 women aged 16 years or older, with advanced endometrial cancer who require further treatment after their initial chemotherapy treatment. Potential participants will be recruited from the hospital setting.

Participants will be allocated to one of the following three trial arms on a 1:1:1 basis using centralised internet randomisation, stratified for prognostic factors:

Arm 1: (Control Arm): Paclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles.

Arm 2: Cediranib 20 mg once daily for 28 days given with weekly paclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles. Participants with stable disease, partial response or complete response at 6 months as determined by RECIST v1.1 will be eligible to continue treatment with single agent cediranib once daily until disease progression.

Arm 3: Cediranib 20 mg once daily with olaparib 300 mg twice daily, continuously on a 28 day cycle for up to 6 cycles. Participants with stable disease, partial response or complete response at 6 months as determined by RECIST v1.1 will be eligible to continue treatment with both olaparib and cediranib until disease progression.

Randomisation will be balanced for histological subtype and the number of chemotherapy regimens for metastatic disease.

Recruitment to the trial is expected to take 30 months. The total duration of the trial is expected to be 55 months. Participants will receive initial trial treatments for up to six months as long as they remain progression free. As mentioned above, participants in the experimental arms may continue treatment with cediranib/olaparib beyond the six months, and beyond the end of the trial, if they remain progression free. The trial will end once all participants have met at least one of the criteria: completed 12 months' follow-up (including treatment), withdrawn from follow-up, been lost to follow-up, experienced disease progression, or died. Participants consent for their medical notes to be reviewed at later dates if required to obtain data such as overall survival.

The trial has a multi-arm-multi-stage (MAMS) design. The appropriate sample size was calculated for this MAMS design, which allows one (or both) ineffective experimental arms to be dropped following a planned interim analysis after 60 participants have been assessed at three months.

Being tested
Paclitaxel, Cediranib, Olaparib
Keywords
Endometrial, Cancer, Paclitaxel, Cediranib, Olaparib
Medical subject headings
Carcinosarcoma, Endometrial Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PaclitaxelDrug

    Also called L01CD01

    80 mg/m2 on three days in a 28 day cycle (with 6 cycles)

  • CediranibDrug

    Also called AZD2171, 288383-20-0

    20 mg per day

  • OlaparibDrug

    Also called AZD2281, Lynparza, L01XX46

    Olaparib tablets, 300 mg twice-daily

Study groups in NCT03570437
Study groupRoleWhat they receive
Arm 1: PaclitaxelActive comparatorPaclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles.
Receives: Drug: Paclitaxel
Arm 2: Cediranib and paclitaxelExperimentalCediranib 20 mg once daily for 28 days given with weekly paclitaxel 80 mg/m2 administered on days 1, 8 and 15 of a 28-day cycle for up to 6 cycles. Participants with stable disease or better will be able to continue cediranib once daily until disease progression.
Receives: Drug: Paclitaxel; Drug: Cediranib
Arm 3: Cediranib and olaparibExperimentalCediranib 20 mg once daily with olaparib 300 mg twice daily, continuously on a 28 day cycle for up to 6 cycles. Participants with stable disease or better will be able to continue with olaparib and cediranib until disease progression.
Receives: Drug: Cediranib; Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    Progression free survival rate at 3 months

    Measured: 3 months

Secondary outcomes (6)

  1. Radiological response rate

    Radiological response rate assessed by RECIST v1.1

    Measured: Assessed from CT scans up to and including the CT scan which shows disease progression, up to 6 months

  2. Median progression free survival (PFS)

    Time from date of randomisation to date of investigator-assessed objective progression via RECIST v1.1 or death from any cause in the absence of progression.

    Measured: From date of randomisation to date of investigator-assessed objective progression via RECIST v1.1 or death from any cause in the absence of progression, up to 42 months

  3. 6-month progression free survival (PFS)

    Proportion of participants free from investigator assessed objective disease progression by RECIST v1.1, or death from any cause, six months from the date of randomisation.

    Measured: 6 months

  4. Toxicities

    Toxicities of any grade associated with each regimen as assessed by CTCAE version 4.03.

    Measured: Up to 30 days after end of treatment

  5. Median overall survival

    Median time from date of randomisation to date of death

    Measured: From date of randomisation to date of death, up to 42 months

  6. Quality of life using a questionnaire

    Quality of life measured using the EORTC QLQ-C30 tool and EN24 endometrial cancer-specific module.

    Measured: Up to 30 days after end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2018
  2. Study start17 May 2018
  3. Primary completion31 Jan 2023 (estimated)
  4. Study completion30 Jun 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomised, three-arm open-label trial with multi-arm-multi-stage (MAMS) design.
Masking
None (open label)
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03570437
Sponsor's protocol ID
R120537
Other IDs
ESR-15-11357, 17/SC/0536, 216069, 2016-004617-28, U1111-1197-9991, 2016
Acronym
COPELIA
Status last verified
Feb 2022
First submitted
31 May 2018
Last updated
2 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Morgan RD, Porter C, Zhou C, Kristeleit R, Desai S, Vazquez I, George A, Eminowicz G, Walther A, Franklin A, Sadozye AH, Hughes A, Hanna L, Roux R, Lord R, Bowen R, Wood J, Sentamans C, White A, Casbard AC, Humphrys A, Swettenham JB, Nixon LS, Adams R, Ray R, Brogden E, Powell WE, Canham J, Cox TM, Narasimham M, Lowe H, Ensell L, Zubair M, Morris K, Glenister-Doyle M, Gassio AF, Morgan D, Broughton D, Carucci M, Monaghan PJ, Tugwood J, Edmondson RJ, Dive C, Jayson GC, Clamp AR. Cediranib with weekly paclitaxel or olaparib versus weekly paclitaxel for advanced or recurrent endometrial cancer (COPELIA): a multicentre, open-label, randomised, phase 2 trial in the UK. EClinicalMedicine. 2026 Jun 16;96:104012. doi: 10.1016/j.eclinm.2026.104012. eCollection 2026 Jun.

    PubMed 42339309

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paclitaxel, Cediranib and Olaparib in people with Carcinosarcoma and Endometrial Neoplasms, run by University of Manchester at 15 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03570437, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.

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