Dose-Escalation Study of Intensity-Modulated Radiotherapy(IMRT)in Patients With Unresectable Pancreatic Cancer

Phase 1

Completed

Interventions: Radiation: INTENSITY MODULATED RADIOTHERAPY
Drug: Gemcitabine

Brief Summary: This is a research study for pancreatic cancer. One way of improving the results of current standard treatments is to try new approaches. This study will examine the use of a more advanced radiation therapy technique, called intensity modulated radiation therapy (IMRT), with chemotherapy. All subjects on this study will be treated with gemcitabine. This chemotherapy agent has been used for patients with pancreatic cancer. The researchers have already done studies using radiation therapy and gemcitabine. They want to build on the information they have from this previous research. The researchers want to find the best dose of IMRT that can be given at the same time that patients are receiving gemcitabine. To do this, they will vary the total dose of radiation received by patients on this study based on the information they have available from previously treated patients. The goal of the research is to identify the highest dose of IMRT that can be given at the same time as the chemotherapy without causing severe side effects.

Recruitment & Eligibility

Inclusion Criteria

Is the patient 18 years of age or older.
Does the patient have histologically or cytologically proven carcinoma of the pancreas
Is the tumor unresectable or medically inoperable
Does the patient have a Zubrod performance status of ≤ 2 (appendix I).
Does the patient have an absolute neutrophil count of ≥ 1500/mm3, and platelets ≥ 100,000/mm3
Does the patient have adequate renal function (creatinine < 2 mg/dl) and hepatic function (bilirubin < 3 mg/dl), with relief of biliary obstruction if present
Is the patient free of significant co-morbid conditions that would preclude safe administration or completion of protocol therapy
If the patient is of reproductive potential, has he or she agreed to use an effective method of contraception during treatment on this trial and for 6 months after treatment
Is the patient aware of the investigational nature of the therapy such that they can provide written informed consent

Exclusion Criteria

Does the patient have a neuroendocrine tumor of the pancreas
Does the patient have metastatic disease
Does the patient have a history of abdominal radiation therapy
Is there history of more than 1 month of therapy with single agent gemcitabine
Has the patient used any investigational agent in the month before enrollment into the study

Arm && Interventions

Group	Intervention	Description
Radiation Dose Escalation with Gemcitabine	INTENSITY MODULATED RADIOTHERAPY	INTENSITY MODULATED RADIOTHERAPY Radiation dose escalation: Total dose Dose per fraction BED\* Dose equivalent (1.8 Gy/fraction) Level 1 45.0 1.8 53.1 45.0 Level 2 50.0 2.0 60.0 50.4 Level 3 52.5 2.1 63.5 54.0 Level 4 55.0 2.2 67.1 57.0 Level 5 57.5 2.3 70.7 60.0 Level 6 60.0 2.4 74.4 63.0 Level 7 62.5 2.5 78.1 66.2 Level 8 65.0 2.6 81.9 69.4 * BED=Biological Effective Dose; =10 Five fractions weekly, fraction size determined by dose level Gemcitabine: 1000mg/m2 will be infused over 100 minutes on days 1, 8, 22 and 29 of the radiation treatment
Radiation Dose Escalation with Gemcitabine	Gemcitabine	INTENSITY MODULATED RADIOTHERAPY Radiation dose escalation: Total dose Dose per fraction BED\* Dose equivalent (1.8 Gy/fraction) Level 1 45.0 1.8 53.1 45.0 Level 2 50.0 2.0 60.0 50.4 Level 3 52.5 2.1 63.5 54.0 Level 4 55.0 2.2 67.1 57.0 Level 5 57.5 2.3 70.7 60.0 Level 6 60.0 2.4 74.4 63.0 Level 7 62.5 2.5 78.1 66.2 Level 8 65.0 2.6 81.9 69.4 * BED=Biological Effective Dose; =10 Five fractions weekly, fraction size determined by dose level Gemcitabine: 1000mg/m2 will be infused over 100 minutes on days 1, 8, 22 and 29 of the radiation treatment

Primary Outcome Measures

Name	Time	Method
The Maximum Tolerated Radiation Dose	13 weeks post radiation	The maximum tolerated radiation dose delivered with intensity-modulated radiotherapy (IMRT) and concurrent gemcitabine in patients with unresectable adenocarcinoma of the pancreas.

Secondary Outcome Measures