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

http://www.cancerresearchuk.org/cancer-help/trials/a-trial-of-nab-paclitaxel-with-gemcitabine-for-cancer-of-pancreas-that-has-spread-siege

Contact information

Dr Katy Dalchau
Scientific

Cambridge Cancer Trials Centre
Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Email katy.dalchau@addenbrookes.nhs.uk

Study information

Study designRandomized interventional study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleRandomised 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 acronymSIEGE
Study objectivesMetastatic 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) studiedTopic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas
InterventionEligible 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Nabpaclitaxel, gemcitabine
Primary outcome measureProgression-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 measures1. 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 date23/01/2014
Completion date01/07/2015

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned Sample Size: 120; UK Sample Size: 120
Total final enrolment146
Key inclusion criteria1. 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 criteria1. 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 enrolment23/01/2014
Date of final enrolment01/07/2015

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Cambridge Cancer Trials Centre
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

ROR logo "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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot 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.