Stereotactic Body Radiotherapy Dose Escalation in Pancreatic Cancer

Study Overview
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Brief Summary
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This study is to determine the maximum tolerated dose (MTD) of five fraction stereotactic radiotherapy (SBRT) in pancreatic cancer.

Detailed Description
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This trial is designed to find the maximum tolerated dose of radiation under a fixed 5-fraction SBRT regimen escalating the dose from 40 Gy in 5 fractions, to 60 Gy in 5 fractions, at 5 Gy intervals.

Official Title
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Phase I Trial of Adaptive Stereotactic Body Radiotherapy (SBRT) Dose Escalation in Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis: Histologically-proven invasive adenocarcinoma of the pancreas. Disease Status: Medically unresectable (any stage), or locally advanced (stage III). Tumor Location: Primary tumor may be located anywhere in the pancreas. Treatment eligibility: The patient must be able to have fiducial markers implanted into the pancreatic tumor, and receive radiation regimen as specified in the protocol. Performance Level: Karnofsky Performance Status ≥ 60 Adequate Renal Function Defined As: Serum creatinine ≤ 1.5 x upper limit of normal Informed Consent: All subjects must sign a written informed consent. Exclusion Criteria: Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events. (Note: Serum Pregnancy tests must be obtained in women of child bearing potential). Sexually active females may not participate unless they have agreed to use an effective contraceptive method (such as abstinence, diaphragm, condom, or intrauterine device) to prevent pregnancy for the duration of the study. Life expectancy < 6 months The patient cannot have had prior radiation therapy to the thorax or upper abdomen. Incarcerated individuals Subjects unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>SBRT 40 Gy in 5 fractions | Radiation: SBRT<br>* Fixed five-fraction stereotactic radiotherapy<br>|
| Experimental: Cohort 2<br>SBRT 45 Gy in 5 fractions (starting dose level) | Radiation: SBRT<br>* Fixed five-fraction stereotactic radiotherapy<br>|
| Experimental: Cohort 3<br>SBRT 50 Gy in 5 fractions | Radiation: SBRT<br>* Fixed five-fraction stereotactic radiotherapy<br>|
| Experimental: Cohort 4<br>SBRT 55 Gy in 5 fractions | Radiation: SBRT<br>* Fixed five-fraction stereotactic radiotherapy<br>|
| Experimental: Cohort 5<br>SBRT 60 Gy in 5 fractions | Radiation: SBRT<br>* Fixed five-fraction stereotactic radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | The purpose of this study is to determine the maximum tolerated dose of five fraction stereotactic radiotherapy (SBRT) in pancreatic cancer. | From date of randomization to observed dose limiting toxicity (DLT) in 20% of patients assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tumor Progression | local tumor control remains a crucial part of treatment for patients with pancreatic cancer who are not candidates for curative therapy. | From date of randomization until local disease progression defined as a ≥20% increase in size on CT compared with CT prior to SBRT assessed over 3 years | 
| Distant Metastatic Progression Rate | The cumulative incidence of distant metastatic failure will be determined for all patients treating death as a competing risk. In patients initially presenting with locally advanced disease, distant disease progression will be defined as the appearance of new metastatic lesions. In patients presenting with metastatic disease, distant progression will be defined as a ≥20% increase in size on CT of the previously noted metastatic lesions. | From date of randomization until the appearance of new lesions or a ≥20% increase in size on CT of the previously noted metastatic lesions assessed over 3 years | 
| Overall Survival | Overall survival will be measured from the date of diagnosis through death of any cause. Survival will also be reported from the date of SBRT for comparisons to other trials in the literature. Finally, survival will be stratified by those with locally advanced disease, and those with metastatic disease on presentation. | From date of diagnosis and SBRT to date of death assessed over 3 years |