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

NCT03570437 | Unknown Phase 2 DMC

• 6 other identifiers: R120537ESR-15-1135717/SC/05362160692016-004617-28U1111-1197-9991
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 15

Brief 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. Participants will be allocated at random to one of three groups:

1. 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. 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. 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.
4. 4.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)
5. 5.Whether the two new treatments cause more or fewer side-effects than standard chemotherapy
6. 6.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
7. 7.Whether we can learn how these treatments work in women with endometrial cancer by taking some additional blood tests for research.

Conditions

Carcinosarcoma; Endometrial Neoplasms

Keywords

Endometrial; Cancer; Paclitaxel; Cediranib; Olaparib

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Progression free survival rate at 3 months

  3 months

Secondary Outcomes (6)

• Radiological response rate

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

• Median progression free survival (PFS)

  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

• 6-month progression free survival (PFS)

  6 months

• Toxicities

  Up to 30 days after end of treatment

• Median overall survival

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

Other Outcomes (3)

• Angiogenesis-related cytokines

  Up to 30 days after end of treatment

• Circulating tumour cells (CTCs)

  From randomisation until up to 30 days after end of treatment

• Gamma H2AX in circulating tumour cells

  From randomisation until up to 30 days after end of treatment

Study Arms (3)

Arm 1: Paclitaxel

ACTIVE COMPARATOR

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

Drug: Paclitaxel

Arm 2: Cediranib and paclitaxel

EXPERIMENTAL

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 or better will be able to continue cediranib once daily until disease progression.

Drug: Paclitaxel; Drug: Cediranib

Arm 3: Cediranib and olaparib

EXPERIMENTAL

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 or better will be able to continue with olaparib and cediranib until disease progression.

Drug: Cediranib; Drug: Olaparib

Interventions

Paclitaxel DRUG

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

Also known as: L01CD01

Arm 1: Paclitaxel; Arm 2: Cediranib and paclitaxel

Cediranib DRUG

20 mg per day

Also known as: AZD2171, 288383-20-0

Arm 2: Cediranib and paclitaxel; Arm 3: Cediranib and olaparib

Olaparib DRUG

Olaparib tablets, 300 mg twice-daily

Also known as: AZD2281, Lynparza, L01XX46

Arm 3: Cediranib and olaparib

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• have received one or two prior lines of cytotoxic chemotherapy for recurrent/ progressive endometrial cancer (not counting adjuvant treatment).
• 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.

You may not qualify if:

• 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.
• 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:
• i. 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)

Sponsors & Collaborators

• University of Manchester: lead
• AstraZeneca: collaborator
• Cardiff University: collaborator

Study Sites (15)

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 7 XX, United Kingdom

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, BA1 3NG, United Kingdom

Location

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

Bristol, BS2 8ED, United Kingdom

Location

Velindre Cancer Centre, Velindre University NHS Trust

Cardiff, CF14 2TL, United Kingdom

Location

Beatson West of Scotland Oncology Centre

Glasgow, G12 0YN, United Kingdom

Location

Airedale NHS Foundation Trust

Keighley, BD20 6TD, United Kingdom

Location

Hope Clinical Trials Facility, Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Guys & St Thomas NHS Trust

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospitals

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Northern Centre for Cancer Care, Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

The Churchill Hospital, Old Road, Headington

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Carcinosarcoma; Endometrial Neoplasms; Neoplasms

Interventions

Paclitaxel; cediranib; olaparib

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Gordon Jayson

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medical Oncology

Model Details: Randomised, three-arm open-label trial with multi-arm-multi-stage (MAMS) design.

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: June 27, 2018
• Study Start: May 17, 2018
• Primary Completion: January 31, 2023
• Study Completion: June 30, 2023
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (15)