Advanced or recurrent endometrial carcinoma or carcinosarcoma MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Olaparib (Lynparza)
Product Name: Olaparib (Lynparza)
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or P
Sponsors
The University of Manchester
Eligibility
Sex/Gender
All
Inclusion criteria
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 0-1. 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 =65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
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 and potential for reactivation during treatment. 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 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: 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) • 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. 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, impending fistulation seen on radiological imaging, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline at screening, and 6- and 12-weeks after randomisation.; Main Objective: The trial is evaluating two new tablet medications; cediranib and olaparib in endometrial cancer. The principal aim of the trial is to find out whether the two new treatments, cediranib tablets with paclitaxel chemotherapy (Arm 2), and cediranib tablets with olaparib tablets (Arm 3), are more effective at treating endometrial cancer than standard paclitaxel chemotherapy (Arm 1). ; Secondary Objective: The other main aims of the trial are to find out: * Whether the two new treatments cause more or fewer side-effects than standard chemotherapy. * 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. * Whether we can learn how these treatments work in women with endometrial cancer by taking some additional blood tests for research. We also want to genetically test some cancer biopsy samples to see if we can predict which women will benefit from olaparib treatment (Arm 3). Only some hospitals are helping us with this part of the study as we need to process the samples quickly. We will ask the permission of women allocated to Arm 3 (cediranib tablets with olaparib tablets) at participating hospitals to take a small biopsy from their cancer before they start treatment. It is optional to donate blood or tissue samples. ;Primary end point(s): The primary outcome measure is progression-free survival (PFS) rate at three months. This is defined as the proportion of participants free from investigator assessed objective disease progression by RECIST v1.1, or death from any cause, three months from the date of randomisation. Measurable disease and non-measurable disease visible on the baseline CT scan will be identifie | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Radiological response rate assessed by RECIST v1.1. 2. Median progression-free survival (PFS) where PFS is measured as the 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. 3. Six-month PFS rate, defined as the 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. 4. Toxicities of any grade associated with each regimen as assessed by CTCAE version 4.03. 5. Median overall survival defined as the time from date of randomisation to date of death. 6. Quality of life measured using the EORTC QLQ-C30 tool and EN24 endometrial cancer-specific module. ; Timepoint(s) of evaluation of this end point: 1, 2. CT scans at screening, 6- and 12-weeks after randomisation, and 12-weekly after that. 3. CT scans at screening, 6-, 12-, 24-weeks after randomisation. 4. Day 1 of each 28 day cycle during treatment, and assessment 30 days after end of treatment. 5. Survival assessed at 3-monthly follow-up until end of trial or death. 6. Quality of life measured at screening, day 1 of each 28 day cycle, monthly until disease progression, and assessment 30 days after end of treatment. | — |
Countries
United Kingdom
Contacts
Public ContactCOPELIA Trial Manager
Centre for Trials Research (CTR)
Outcome results
None listed