Gemcitabine, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery

Pancreatic Cancer Clinical Trial

— SCALOP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01032057
• Other study ID #: CDR0000660755
• Secondary ID: WCTU-SCALOPEUDRA
• Status: Completed
• Phase: Phase 2
• Start date: July 2009
• Est. completion date: June 2013

Study information

• Verified date: October 2018
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• capecitabine

• gemcitabine hydrochloride

Procedure:
• quality-of-life assessment

Radiation:
• 3-dimensional conformal radiation therapy

Locations

Country	Name	City	State
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Queen Alexandra Hospital	Cosham	England
United Kingdom	Castle Hill Hospital	Cottingham	England
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Royal Free Hospital	London	England
United Kingdom	Northampton General Hospital	Northampton	England
United Kingdom	Perth Royal Infirmary	Perth	Scotland
United Kingdom	Edith Cavell Hospital	Peterborough
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Musgrove Park Hospital	Taunton	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales

Sponsors (1)

Lead Sponsor	Collaborator
Lisette Nixon

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

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 — View 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 O — View 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 locall — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 39 weeks (from registration) according to RECIST criteria		Assessed 39 weeks from registration
Secondary	Toxicity according to NCI CTCAE v.3.0		Assessed throughout trial treatment and follow-up
Secondary	Quality of life as measured by questionnaires QLQ-C30 and PAN26 at baseline and at 17, 23, 26, 39, and 52 weeks		Assessed throughout trial treatment and follow-up
Secondary	Overall survival at 52 weeks and time from registration to death by any cause		Assessed 52 weeks post registration and during NHS flagging
Secondary	Objective disease response according to RECIST criteria		39 weeks post registration
Secondary	Progression-free survival (time to event) according to RECIST criteria		Assessed during NHS flagging at the end of the trial
Secondary	Radiotherapy quality assurance (adherence to protocol)		Upon completion of the trial