Clinical trial NCT01360593
Conditions: Pancreatic Cancer
Keywords: Pancreas
Sponsor: David A. Clump, MD, PhD
Start date: 2011-07-25; Completion date: 2018-10-01
Enrollment: 35 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The current study seeks to further investigate the impact of up-front systemic therapy in combination with fractionated SBRT for potentially resectable, locally-advanced pancreatic adenocarcinoma.

Detailed description:
All subjects will have a baseline CT or FDG-PET/CT prior to initiation of therapy. This will be done at the Hillman or in Radiation Oncology. Enrolled patients will undergo appropriate lab work and staging as described

1. Albumin, alkaline phosphatase, glucose, electrolytes
2. Ca 19-9 and CEA
3. Due to an interaction of capecitabine and oral coumadin-derivative anticoagulants and risk of bleeding/thrombotic events, if a patient is on coumadin, frequent monitoring of INR and dose adjustments of anticoagulants must be exercised during protocol treatment. Alternatively, low molecular weight heparin may be substituted for oral anticoagulants Chemotherapy will be initiated consisting of gemcitabine 1000mg/m2 IV on day 1 and 8 of a 21 day cycle. Dosage for gemcitabine is described below using the Body surface area (BSA).

BSA will be calculated from body weight in kg, recorded prior to every gemcitabine dosing, and height in cm, recorded at baseline.

Premedication for Gemcitabine

A standard, FDA-approved antiemetic medication will be administered to study participants at the discretion of the treating oncologist (investigator) one-half hour prior to the gemcitabine infusion. Examples of standard antiemetics include ondansetron (Zofran), granisetron (Kytril), dolasetron (Anzemet), compazine, and dexamethasone. The dosage and route of administration will be determined by the treating oncologist based upon the given clinical scenario.

In addition, capecitabine 650mg/m2 PO will be taken twice daily on days 1-14 of a 3 week cycle. Four cycles total (12 weeks) of chemotherapy will be given. Dosage for capecitabine is described below using the Body surface area (BSA).

BSA will be calculated from body weight in kg, recorded prior to every capecitabine dosing, and height in cm, recorded at baseline.

Capecitabine (Xeloda; F. Hoffmann-La Roche AG, Basel, Switzerland) is supplied as ﬁlm-coated tablets in two dose strengths (150 and 500 mg); the closest practical dose (by rounding up or down) calculated on body-surface area based on a combination of tablets is taken within 30 minutes after the end of a meal.

Patients will be assessed during chemotherapy with appropriate dose modifications made based on toxicity. Following the completion of chemotherapy, a new FDG-PET/CT or CT will be obtained to assess response and plan for SBRT. For those patients with SD, PR, or CR, SBRT will be planned and delivered.

Fidiucial placement In addition, all patients will have fiducial markers placed for localization at time of SBRT. Three to five soft-tissue fiducials (markers) will be placed in and/or around the tumor, at least 1cm apart. Oftentimes, these are placed at the time of endoscopic ultrasound and biopsy for diagnosis. If that is not the case, patients will be scheduled for a repeat EUS and have the markers placed prior to CT or FDG-PET/CT simulation. Alternatively, fiducials may be placed at the time of staging laparoscopy.

Stereotactic Body Radiotherapy Planning SBRT will be done in Shadyside Radiation Oncology.

An SBRT plan will be created based on the disease contoured on the CT and PET. The plan will be to deliver fractionated SBRT to the isodose line best encompassing the PTV:

12 Gy x 3 fractions (36 Gy total)

Careful evaluation of the each plan will be conducted by the radiosurgical team to ensure that normal tissues and critical structures tolerances are maintained.

The maximum dose (in Gy) within the treatment volume (MD), prescriptions dose (PD), and the ratio of MD/PD (as a measure of heterogeneity within the target volume), prescription isodose volume (PIV in mm3), tumor volume (TV in mm3), and the ratio of PIV/TV (as a measure of dose conformity of the treatment relative to the target) will be recorded.

Quality of Life Assessment Quality of life assessment using the Functional Assessment of Cancer Therapy - General (FACT-G) tool, which is a validated tool, will be administered to all subjects prior to treatment and at each follow-up visit.

For patients with potentially resectable tumors, they will be assessed 10 - 12 weeks after SBRT by a multidisciplinary team including two expert pancreas surgeons and by FDG-PET/CT or CT scan. If deemed appropriate, patients with an adequate response will be taken for surgical resection. This will be performed as standard care.

Time frames for chemotherapy and SBRT for 4 cycles of gemcitabine and capecitabine. The SBRT will not start until twelve weeks after the chemotherapy stops and will last approximately one week. Each cycle of gemcitabine and capecitabine is three weeks. Upon completion of treatment patients will be followed for survival for 24 months. They will be in the study for approximately two years give or take a few months.

Interim medical history and physical examination 4 - 6 weeks after SBRT.

Serum chemistry and electrolytes to include BUN, creatinine, sodium, potassium, bicarbonate, chloride, calcium, magnesium, glucose, total bilirubin, AST, ALT, alkaline phosphatase prior to chemotherapy treatments, 4 -6 weeks post-SBRT treatment, and then at follow-up as clinically indicated

Hematologic studies to include CBC with differential and platelet count weekly during chemotherapy sessions and then repeated 4-6 weeks post-SBRT treatment and then at follow-up as clinically indicated

CT or FDG-PET/CT scans (for consistency procedure done at screening/planning will continue in follow-up) will be obtained at 10-12 weeks post-treatment and will be reviewed for evidence of response. Subjects who demonstrate no evidence of distant metastases and meet RECIST criteria of partial response, complete response, or stable disease will be offered surgical exploration and attempted curative resection. Subjects demonstrating unresectable disease or progression of disease will be started on systemic chemotherapy at the discretion of the treating medical oncologist.

Arms: arm 1: None
Interventions: intervention 1: Gemcitabine intervention 2: Capecitabine intervention 3: Stereotactic Body Radiation Therapy (SBRT)
Intervention descriptions: intervention 1: Gemcitabine will be administered for 2 weekly doses every 3 weeks commencing 12 weeks prior to stereotactic radiosurgery as follows:

Gemcitabine 1,000 mg/m2 IV over 30 minutes on Day 1, and 8 of 21- day cycle. This will be done for up to 4 cycles. intervention 2: Capecitabine will be taken orally twice daily on days 1-14 every 3 weeks for 4 cycles (12 weeks) prior to stereotactic radiosurgery as follows:

Capecitabine 650 mg/m2 twice daily for days 1-14 every 3 weeks for up to 4 cycles. intervention 3: Fractionated SBRT will be delivered to patients that have stable disease, partial response, or complete response after chemo in the following manner:

12 Gy x 3 fractions (36 Gy total) This will be given every other day.

Protocol documents: