Scheduling nabpaclItaxel with gemcitabine (SIEGE)
| ISRCTN | ISRCTN71070888 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71070888 |
| EudraCT/CTIS number | 2013-001868-40 |
| ClinicalTrials.gov number | NCT03529175 |
| Secondary identifying numbers | 15344 |
- Submission date
- 08/05/2014
- Registration date
- 08/05/2014
- Last edited
- 24/02/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr Katy Dalchau
Scientific
Scientific
Cambridge Cancer Trials Centre
Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom
| katy.dalchau@addenbrookes.nhs.uk |
Study information
| Study design | Randomized interventional study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Randomised phase II trial to investigate two different schedules of nab-paclitaxel (Abraxane) combined with gemcitabine as first line treatment for metastatic pancreatic ductal adenocarcinoma |
| Study acronym | SIEGE |
| Study objectives | Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis. The concomitant ABX/GEM chemotherapy regimen has been shown to improve overall survival over the standard single agent GEM. Studies in mouse models of PDAC suggest that delivery of ABX 24 hours prior to GEM might result in higher intra-tumoural GEM concentrations. SIEGE is looking at the how the scheduling of these two drugs may be critical to optimising clinical benefit. |
| Ethics approval(s) | Approved 01/11/2013, Office for Research Ethics Committees Northern Ireland, ref: 13/NI/0143 |
| Health condition(s) or problem(s) studied | Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas |
| Intervention | Eligible patients are randomly assigned via a web-based randomisation system to either the concomitant ABX/GEM arm or the sequential ABX/GEM arm in a 1:1 ratio using the stratified block randomisation method. Stratification factors are original primary site of disease (head versus body and/or tail) and presence of liver metastases (yes versus no). Abraxane administration: On days 1, 8 and 15 of a 4 weekly cycle Gemcitabine administration: On days 1, 8, 15 or days 2, 9 and 16 of a 4-weekly cycle dependent upon the arm; Follow Up Length: 12 month(s) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Nabpaclitaxel, gemcitabine |
| Primary outcome measure | Progression-free survival is calculated from the date of randomisation to the date of clinical/radiological progression or death from any cause, whichever occurs first |
| Secondary outcome measures | 1. Health economics (HE); Timepoint(s): 4-weekly 2. Overall survival; Timepoint(s): 3-monthly 3. Quality of life (QoL); Timepoint(s): 4-weekly 4. Response; Timepoint(s): 8-weekly 5. Safety; Timepoint(s): 4-weekly Efficacy is measured by 1. Objective response: response will be assessed according to RECIST version 1.1 2. Disease control 3. Overall survival, calculated from date of randomisation to the date of death from any cause; surviving patients will be censored at the date last known alive. Safety is measured via 1. Adverse Events (including Serious Adverse Events) assessed using NCI CTCAE version 4.03 2. Laboratory test results 3. Karnofsky performance status, ECOG performance status, vital signs and physical examination Exploratory Outcome Measures via 1. Quality of life questionnaires (EORTC QLQ-C30, QLQ-PAN26) 2. Health Economics questionnaires (EQ-5D-5L) |
| Overall study start date | 23/01/2014 |
| Completion date | 01/07/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 120; UK Sample Size: 120 |
| Total final enrolment | 146 |
| Key inclusion criteria | 1. Aged >= 18 years old 2. Signed informed consent and ability to comply with the protocol 3. Histologically or cytologically confirmed metastatic PDAC 4. Radiologically confirmed stage IV disease and measurable disease by RECIST version 1.1; baseline tumour assessments and measurements must be done within 28 days prior to randomisation 5. Karnofsky performance status =70% 6. Life expectancy >12 weeks from the date of screening assessment Adequate bone marrow function 6.1. Absolute neutrophil count (ANC) =1.5 x 10^9 /L 6.2. Haemoglobin (Hb) = 100 g/L 6.3. Platelets =100 x 10^9 /L 6.4. White blood cell count (WBC) = 3 x 10^9 /L 7. Adequate liver function 7.1. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =2.5 x upper limit of normal range (ULN) 7.2. Total bilirubin <1.5 x ULN 8. Adequate renal function defined as a serum creatinine =1.5 x ULN or calculated creatinine clearance by CockcroftGaultv of =50 mL/min 9. Received no prior systemic therapy for metastatic disease 10. Prior adjuvant chemotherapy (with GEM or any other drug/s) is allowed if completed at least 6 months previously 11. Prior radiotherapy is allowed as long as there is measurable disease which has not been irradiated 12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and HE questionnaires and other study procedures 13. Confirmation of tumour tissue sample collected within 12 weeks prior to randomisation and blood to be taken prior to randomisation 14. Women of childbearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not postmenopausal for at least 24 consecutive months if age =55 years or 12 months if age >55 years, must have a negative serum or urine pregnancy test within 14 days prior to randomisation 15. All WCBP, all sexually active male patients, and all partners of patients must agree to use effective contraception methods throughout the study and for 30 days after the final dose of study drug for WCBP and for up to 6 months after treatment for male patients |
| Key exclusion criteria | 1. Patients with operable or locally advanced PDAC 2. Other invasive malignancies diagnosed within the last 5 years, except nonmelanoma skin cancer and localized cured prostate cancer 3. Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to: 3.1. Patients who have had a venous thromboembolic event who are not appropriately anticoagulated or have had a significant bleeding episode in the 3 weeks prior to randomisation 3.2. Patients with symptoms of severe chronic obstructive airways disease or significant shortness of breath at rest AND have an FEV1<1.0 L within the last 6 months 3.3. Patients with a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis 3.4. Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months 3.5. Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV) or frequent angina 3.6. Presence of active infection 3.7. Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C 3.8. Known allergy or hypersensitivity to GEM or ABX 4. Women who are pregnant, plan to become pregnant or are lactating 5. Use of oral antioxidant supplements: betacarotene, selenium, lutein, zeaxanthin, lycopene, pycnogenol, fernblock, omega3S, vitamin C, vitamin E, astaxanthin |
| Date of first enrolment | 23/01/2014 |
| Date of final enrolment | 01/07/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cambridge Cancer Trials Centre
Cambridge
CB2 0QQ
United Kingdom
CB2 0QQ
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Industry
Celgene Europe Ltd (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | results abstract, 2017 Gastrointestinal Cancers Symposium | 01/02/2017 | No | No | |
| Results article | Results | 22/02/2023 | 24/02/2023 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
24/02/2023: Publication reference and total final enrolment added.
05/08/2019: ClinicalTrials.gov number added.
10/08/2017: Publication reference added.
