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

Lisette Nixon

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Radiation: 3-dimensional conformal radiation therapy; Procedure: quality-of-life assessment; Drug: capecitabine; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT01032057

EUDRACT-2008-001394-15

EU-21114

WCTU-SCALOP

CRUK-07/040

WCTU-SPON-415-07

CDR0000660755

ISRCTN-96169987

Details and patient eligibility

About

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.

Full 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.

Enrollment: 114 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 2 patient groups

Gemcitabine

Active Comparator group

Description:

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)

Treatment:

Procedure: quality-of-life assessment

Radiation: 3-dimensional conformal radiation therapy

Drug: capecitabine

Drug: gemcitabine hydrochloride

chemoradiotherpay with capecitabine

Active Comparator group

Description:

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-Friday)

Treatment:

Procedure: quality-of-life assessment

Radiation: 3-dimensional conformal radiation therapy

Drug: capecitabine

Drug: gemcitabine hydrochloride