Scheduling Nab-paclitaxel With Gemcitabine

NCT03529175 | Completed Phase 2 DMC

• 1 other identifier: SIEGE (AX-PANC-PI-0101)
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 23

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.

Conditions

Pancreatic Adenocarcinoma Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  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.

  From participant randomisation to the point at which disease progression is reported (i.e. 12 months)

Secondary Outcomes (2)

• Patient Safety

  1 year after end of treatment visit

• Treatment Efficacy

  8 weeks

Study Arms (2)

Concomitant

ACTIVE COMPARATOR

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.

Drug: Abraxane (nab-paclitaxel); Drug: Gemcitabine

Sequential

ACTIVE COMPARATOR

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.

Drug: Abraxane (nab-paclitaxel); Drug: Gemcitabine

Interventions

Abraxane (nab-paclitaxel) DRUG

Concomitant; Sequential

Gemcitabine DRUG

Concomitant; Sequential

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CCTU- Cancer Theme: lead
• Celgene: collaborator

Study Sites (23)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Peterborough City Hospital

Peterborough, Cambridgeshire, PE3 9GZ, United Kingdom

Location

Ysbyty Gwynedd

Bangor, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Bristol Haematology & Oncology Centre

Bristol, United Kingdom

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Colchester Hospital

Colchester, CO4 5JL, United Kingdom

Location

University Hospitals Coventry & Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

Edinburgh Cancer Research Centre

Edinburgh, United Kingdom

Location

The Beatson Oncology Centre

Glasgow, United Kingdom

Location

The Royal Surrey County Hospital

Guildford, United Kingdom

Location

St James' Institute of Oncology

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

Barts Health NHS Trust

London, EC1A 7BE, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

The Royal Free Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Related Publications (2)

• Dayimu A, Di Lisio L, Anand S, Roca-Carreras I, Qian W, Al-Mohammad A, Basu B, Valle JW, Jodrell D, Demiris N, Corrie P. Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma. Br J Cancer. 2023 May;128(9):1672-1680. doi: 10.1038/s41416-023-02170-9. Epub 2023 Feb 22.

  PMID: 36813867 DERIVED

• 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.

  PMID: 32350413 DERIVED

Related Links

• University of Cambridge Pancreatic Cancer Centre

MeSH Terms

Interventions

Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Pippa Corrie

  Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CCTU-Cancer Theme

Study Record Dates

• First Submitted: May 1, 2014
• First Posted: May 18, 2018
• Study Start: January 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 16, 2019

Record last verified: 2019-07

Locations

GB (23)