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Scheduling Nab-paclitaxel With Gemcitabine (SIEGE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03529175
Recruitment Status : Completed
First Posted : May 18, 2018
Last Update Posted : July 16, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE May 1, 2014
First Posted Date  ICMJE May 18, 2018
Last Update Posted Date July 16, 2019
Study Start Date  ICMJE January 2014
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
Progression free survival [ Time Frame: From participant randomisation to the point at which disease progression is reported (i.e. 12 months) ]
The primary objective of the trial is to investigate the outcome of sequential administration of nab-paclitaxel combined with gemcitabine (ABX/GEM, 24 hours apart) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in terms of progression-free survival.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
  • Patient Safety [ Time Frame: 1 year after end of treatment visit ]
    Adverse Events (including Serious Adverse Events), abnormal laboratory test results and performance status
  • Treatment Efficacy [ Time Frame: 8 weeks ]
    response to treatment assessed using radiological RECIST criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Scheduling Nab-paclitaxel With Gemcitabine
Official Title  ICMJE 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
Brief Summary

Metastatic pancreatic cancer is difficult to treat. Until recently, most patients would be offered treatment with a chemotherapy drug called gemcitabine. However, a large international trial showed that combining gemcitabine with a drug called nab-paclitaxel (or abraxane) was more effective compared with gemcitabine alone. The purpose of this study is to compare two different ways of combining gemcitabine with abraxane. Conventionally, both drugs are given on the same day via a drip into a vein in the arm but research suggests that giving abraxane 24 hours in advance of gemcitabine could possibly be more beneficial.

In this study, blood and tumour samples will be collected and analysed to try to confirm what has been seen in the laboratory studies. In addition, the investigators wish to find out whether certain tumour characteristics (called biomarkers) can be used to predict for response to chemotherapy.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Adenocarcinoma Metastatic
Intervention  ICMJE
  • Drug: Abraxane (nab-paclitaxel)
  • Drug: Gemcitabine
Study Arms  ICMJE
  • Active Comparator: Concomitant
    Intravenous Abraxane125 mg/m2 30-minute infusion followed immediately by intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle.
    Interventions:
    • Drug: Abraxane (nab-paclitaxel)
    • Drug: Gemcitabine
  • Active Comparator: Sequential
    Intravenous Abraxane 125 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle. Intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 2, 9 and 16 of a 4-week cycle. Gemcitabine must be delivered 24 +/- 2 hours after commencing Abraxane infusion.
    Interventions:
    • Drug: Abraxane (nab-paclitaxel)
    • Drug: Gemcitabine
Publications * Corrie PG, Qian W, Basu B, Valle JW, Falk S, Lwuji C, Wasan H, Palmer D, Scott-Brown M, Wadsley J, Arif S, Bridgewater J, Propper D, Gillmore R, Gopinathan A, Skells R, Bundi P, Brais R, Dalchau K, Bax L, Chhabra A, Machin A, Dayim A, McAdam K, Cummins S, Wall L, Ellis R, Anthoney A, Evans J, Ma YT, Isherwood C, Neesse A, Tuveson D, Jodrell DI. Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma. Br J Cancer. 2020 Jun;122(12):1760-1768. doi: 10.1038/s41416-020-0846-2. Epub 2020 Apr 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2018)
146
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged ≥ 18 years old
  • Signed informed consent and ability to comply with the protocol
  • Histologically or cytologically confirmed metastatic PDAC
  • Radiologically confirmed stage IV disease and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; baseline tumour assessments and measurements must be done within 28 days prior to randomisation
  • Karnofsky performance status ≥70%
  • Life expectancy >12 weeks from the date of screening assessment
  • Adequate bone marrow function

    • Absolute neutrophil count (ANC) ≥1.5 x 109 /L
    • Haemoglobin (Hb) ≥ 100 g/L
    • Platelets ≥100 x 109 /L
    • White blood cell count (WBC) ≥ 3 x 109 /L
  • Adequate liver function

    • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN)
    • Total bilirubin <1.5 x ULN
  • Adequate renal function defined as a serum creatinine ≤1.5 x ULN or calculated creatinine clearance by Cockcroft-Gault of ≥50 mL/min
  • Received no prior systemic therapy for metastatic disease
  • Prior adjuvant chemotherapy (with GEM or any other drug/s) is allowed if completed at least 6 months previously
  • Prior radiotherapy is allowed as long as there is measurable disease which has not been irradiated
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and HE questionnaires and other study procedures
  • Confirmation of tumour tissue sample collected within 12 weeks prior to randomisation and blood to be taken prior to randomisation
  • Women of child-bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal 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
  • All WCBP and all sexually active male 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

Exclusion Criteria:

  • Patients with operable or locally advanced PDAC
  • Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate cancer
  • 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:

    • 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
    • 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
    • Patients with a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis
    • 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
    • Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV, see Appendix 3) or frequent angina
    • Presence of active infection
    • Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C
    • Known allergy or hypersensitivity to GEM or ABX
  • Women who are pregnant, plan to become pregnant or are lactating
  • Routine use of any of the following will exclude patients:

    • Oral anti-oxidant supplements: beta-carotene, selenium, lutein, zeaxanthin, lycopene, pycnogenol, fernblock, omega-3S, vitamin C, vitamin E, astaxanthin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03529175
Other Study ID Numbers  ICMJE SIEGE (AX-PANC-PI-0101)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust
Study Sponsor  ICMJE CCTU- Cancer Theme
Collaborators  ICMJE Celgene
Investigators  ICMJE
Principal Investigator: Pippa Corrie Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
PRS Account Cambridge University Hospitals NHS Foundation Trust
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP