Gemcitabine, Capecitabine, And Radiation Therapy In Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview

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

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.

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.

Pancreatic Cancer

DRUG: capecitabine
DRUG: gemcitabine hydrochloride
PROCEDURE: quality-of-life assessment
RADIATION: 3-dimensional conformal radiation therapy

CDR0000660755
WCTU-SCALOP
EUDRACT-2008-001394-15
ISRCTN-96169987
WCTU-SPON-415-07
CRUK-07/040
EU-21114

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-12-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2018-10-25
First Submitted that Met QC Criteria 2009-12-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2018-10-26
First Posted (ACTUAL) 2009-12-15	Results First Posted N/A	Last Verified 2018-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Gemcitabine GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po) followed by gemcitabine 300mg/m2 weekly (IV) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Friday)	DRUG: capecitabine DRUG: gemcitabine hydrochloride PROCEDURE: quality-of-life assessment RADIATION: 3-dimensional conformal radiation therapy
ACTIVE_COMPARATOR: chemoradiotherpay with capecitabine GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po), followed by capecitabine 830mg/m2 bd (po, Mon-Fri) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Fr	DRUG: capecitabine DRUG: gemcitabine hydrochloride PROCEDURE: quality-of-life assessment RADIATION: 3-dimensional conformal radiation therapy

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Gemcitabine

GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po) followed by gemcitabine 300mg/m2 weekly (IV) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Friday)

DRUG: capecitabine

DRUG: gemcitabine hydrochloride

PROCEDURE: quality-of-life assessment

RADIATION: 3-dimensional conformal radiation therapy

ACTIVE_COMPARATOR: chemoradiotherpay with capecitabine

GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po), followed by capecitabine 830mg/m2 bd (po, Mon-Fri) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Fr

DRUG: capecitabine

DRUG: gemcitabine hydrochloride

PROCEDURE: quality-of-life assessment

RADIATION: 3-dimensional conformal radiation therapy

Primary Outcome Measures	Measure Description	Time Frame
Progression-free survival at 39 weeks (from registration) according to RECIST criteria		Assessed 39 weeks from registration

Secondary Outcome Measures	Measure Description	Time Frame
Toxicity according to NCI CTCAE v.3.0		Assessed throughout trial treatment and follow-up
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
Overall survival at 52 weeks and time from registration to death by any cause		Assessed 52 weeks post registration and during NHS flagging
Objective disease response according to RECIST criteria		39 weeks post registration
Progression-free survival (time to event) according to RECIST criteria		Assessed during NHS flagging at the end of the trial
Radiotherapy quality assurance (adherence to protocol)		Upon completion of the trial

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Somnath Mukherjee, Northampton General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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.
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.

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