Clinical trial NCT01032057: Gemcitabine, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery
Official title: A Multi-Center Randomized Phase II Study of Induction Chemotherapy Followed by Gemcitabine or Capecitabine Based Chemoradiotherapy for Locally Advanced Non-Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage II pancreatic cancer
stage III pancreatic cancer
Lead sponsor: Cardiff University
Sponsor class: OTHER
First posted: 2009-12-15
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. It is not yet known which regimen of chemotherapy given together with radiation therapy is more effective in treating pancreatic cancer.

PURPOSE: This randomized phase II trial is comparing the side effects of two regimens of gemcitabine and capecitabine given together with radiation therapy and to see how well they work in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

* To evaluate the activity, safety, and feasibility of induction chemotherapy comprising gemcitabine and capecitabine followed by two different schedules of chemoradiotherapy comprising gemcitabine or capecitabine and radiotherapy in patients with locally advanced, nonmetastatic, unresectable pancreatic cancer.
* To determine which of the two experimental arms gives the highest generic and disease-specific aspects of health-related quality of life (HRQL) following treatment.
* To determine how HRQL varies during treatment and follow up in both arms.

OUTLINE: This is a multicenter study.

All patients receive a first induction therapy comprising gemcitabine IV on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Following the first induction therapy, patients with a WHO performance status of 0-1 who are responding or have stable disease that can be encompassed within a radically treatable radiotherapy volume are randomized to 1 of 2 treatment arms.

* Arm I:

  * Second induction therapy (weeks 13-16): Patients receive gemcitabine IV once daily on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21.
  * Chemoradiotherapy (weeks 17-22): Patients receive gemcitabine IV once weekly on day 1 and undergo conformal radiotherapy 5 days a week for 5.5 weeks.
* Arm II:

  * Second induction therapy (weeks 13-16): Patients receive gemcitabine IV once daily on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21.
  * Chemoradiotherapy (weeks 17-22): Patients receive oral capecitabine twice daily on days 1-5 and undergo conformal radiotherapy 5 days a week for 5.5 weeks.

Patients complete quality-of-life questionnaires QLQ-C30 and PAN26 at baseline and at 17, 23, 26, 39, and 52 weeks.

After completion of study treatment, patients are followed every 3 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas

  * Locally advanced, nonmetastatic, inoperable, or operable (but medically unfit for surgery) disease

    * Palliative bypass procedure allowed
    * Common bile duct stenting allowed
* Primary pancreatic lesion ≤ 7 cm in diameter as measured by CT scan of the thorax and abdomen within 4 weeks prior to registration
* No recurrent cancer following definitive pancreatic surgery

PATIENT CHARACTERISTICS:

* WHO performance status (PS) 0-2
* Neutrophil count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Hemoglobin ≥ 10 g/dL
* Serum bilirubin \< 35 μmol/L (50 μmol/L allowed for patients who have had a recent biliary drain and whose bilirubin is descending)
* AST/ALT ≤ 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 5 times ULN
* GFR \> 50 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 weeks after completion of study therapy
* No evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease
* No myocardial infarction or stroke within the past 6 months
* No prior malignancies within the past 5 years except for carcinoma in situ of the cervix, adequately treated basal cell skin carcinoma, or any early-stage malignancy
* No suspected DPD deficiency
* No renal abnormalities (e.g., adult polycystic kidney disease, hydronephrosis, or ipsilateral single kidney)
* Must meet the following additional criteria for randomization:

  * WHO PS 0-1
  * Loss of weight no greater than 10% of that at baseline

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 4 weeks since prior and no concurrent sorivudine or analogues
* No prior radiotherapy to the upper abdomen
* No concurrent methotrexate
* No concurrent allopurinol

Primary outcomes:
measure: Progression-free survival at 39 weeks (from registration) according to RECIST criteria
timeFrame: Assessed 39 weeks from registration
Secondary outcomes:
measure: Toxicity according to NCI CTCAE v.3.0
timeFrame: Assessed throughout trial treatment and follow-up
measure: Quality of life as measured by questionnaires QLQ-C30 and PAN26 at baseline and at 17, 23, 26, 39, and 52 weeks
timeFrame: Assessed throughout trial treatment and follow-up
measure: Overall survival at 52 weeks and time from registration to death by any cause
timeFrame: Assessed 52 weeks post registration and during NHS flagging
measure: Objective disease response according to RECIST criteria
timeFrame: 39 weeks post registration
measure: Progression-free survival (time to event) according to RECIST criteria
timeFrame: Assessed during NHS flagging at the end of the trial
measure: Radiotherapy quality assurance (adherence to protocol)
timeFrame: Upon completion of the trial
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cosham
country: United Kingdom
facility: Queen Alexandra Hospital
state: England
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Perth
country: United Kingdom
facility: Perth Royal Infirmary
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
city: Peterborough
country: United Kingdom
facility: Edith Cavell Hospital
Study officials:
affiliation: Northampton General Hospital
name: Somnath Mukherjee
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. Lancet Oncol. 2013 Apr;14(4):317-26. doi: 10.1016/S1470-2045(13)70021-4. Epub 2013 Mar 6.
citation: Fokas E, Spezi E, Patel N, Hurt C, Nixon L, Chu KY, Staffurth J, Abrams R, Mukherjee S. Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial. Radiother Oncol. 2016 Aug;120(2):212-6. doi: 10.1016/j.radonc.2016.07.002. Epub 2016 Aug 3.
citation: Fokas E, Clifford C, Spezi E, Joseph G, Branagan J, Hurt C, Nixon L, Abrams R, Staffurth J, Mukherjee S. Comparison of investigator-delineated gross tumor volumes and quality assurance in pancreatic cancer: Analysis of the pretrial benchmark case for the SCALOP trial. Radiother Oncol. 2015 Dec;117(3):432-7. doi: 10.1016/j.radonc.2015.08.026. Epub 2015 Aug 29.