Clinical trial NCT03529175: Scheduling Nab-paclitaxel With Gemcitabine
Official 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma Metastatic
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2018-05-18
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: From participant randomisation to the point at which disease progression is reported (i.e. 12 months)
Secondary outcomes:
measure: Patient Safety
timeFrame: 1 year after end of treatment visit
measure: Treatment Efficacy
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
state: Cambridgeshire
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Colchester
country: United Kingdom
facility: Colchester Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Research Centre
city: Glasgow
country: United Kingdom
facility: The Beatson Oncology Centre
city: Guildford
country: United Kingdom
facility: The Royal Surrey County Hospital
city: Leeds
country: United Kingdom
facility: St James' Institute of Oncology
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
name: Pippa Corrie
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.