Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Katy Dalchau
ORCID ID
Contact details
Cambridge Cancer Trials Centre
Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom
katy.dalchau@addenbrookes.nhs.uk
Additional identifiers
EudraCT number
2013-001868-40
ClinicalTrials.gov number
Protocol/serial number
15344
Study information
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
Acronym
SIEGE
Study hypothesis
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
Office for Research Ethics Committees Northern Ireland; 01/11/2013; ref. 13/NI/0143
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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).
one of the two treatment arms.
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
Phase
Phase II
Drug names
nabpaclitaxel (Abraxane), gemcitabine
Primary outcome measures
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 trial start date
23/01/2014
Overall trial end date
01/07/2015
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 120; UK Sample Size: 120
Participant exclusion criteria
The presence of any of the following will exclude patients:
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
Recruitment start date
23/01/2014
Recruitment end date
01/07/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cambridge Cancer Trials Centre
Cambridge
CB2 0QQ
United Kingdom
Funders
Funder type
Industry
Funder name
Celgene Europe Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary