3-AP and Radiation Therapy in Treating Patients With Stage III Pancreatic Cancer That Cannot Be Removed By Surgery
This phase I trial is studying the side effects and best dose of 3-AP when given together with radiation therapy in treating patients with stage III pancreatic cancer that cannot be removed by surgery.
3-AP may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. 3-AP may make tumor cells more sensitive to radiation therapy. Giving 3-AP together with radiation therapy may kill more tumor cells.
Stage III Pancreatic Cancer
Radiation: 3-Dimensional Conformal Radiation Therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Triapine® in Combination With Radiation Therapy in Locally Advanced Pancreas Cancer|
- MTD as assessed by the number of patients with dose-limiting toxicity (DLT) [ Time Frame: Observed clinically for 3-4 hours after each 3-AP infusion during the first week of treatment ] [ Designated as safety issue: Yes ]MTD will be the dose at which 1 or fewer patients (less than or equal to 1/6) experiences a DLT during the treatment cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing DLT. DLT will be defined as greater than or equal to Grade 3 non-hematologic or greater than or equal to Grade 4 hematologic adverse event with the following exceptions: greater than or equal to Grade 3 nausea and greater than or equal to Grade 3 vomiting that improves with antiemetic therapy greater than or equal to Grade 3 diarrhea that improves with Lomotil.
- Therapeutic response as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: CT scans at baseline and 4 weeks from end of therapy and then every 2 months for 1 year from start of therapy. Confirmatory scans will also be obtained 2 months following initial documentation of an objective response. ] [ Designated as safety issue: No ]Complete Response (CR) is the disappearance of all target lesions. Partial Response (PR) requires at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The results will be purely descriptive.
- Radiographic correlates using secretin-stimulated MRCP and dynamic contrast enhanced MRI [ Time Frame: Prior to treatment (baseline), 2 weeks within and 4 weeks after combined-modality therapy ] [ Designated as safety issue: No ]The subjects will be imaged with conventional T2- and T1-weighted sequences prior to contrast agent application and with T1-weighted sequences after contrast agent application for tumor localization and volumetry. Dynamic contrast enhanced (DCE) images will be acquired to demonstrate tumor heterogeneity, microcirculation, vascularization and viability. Secretin-stimulated images will be acquired to quantify the functional status of the pancreas. The results will be purely descriptive.
- Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP [ Time Frame: Immediately before and after 3-AP on the first and last day of treatment ] [ Designated as safety issue: No ]The effect of 3-AP on dCTP levels in PBMCs will be evaluated using either a paired t-test or its nonparametric equivalent, the Wilcoxon matched pairs signed ranks test. Assuming normality, a paired t-test will allow us to detect an effect size of approximately 1.0 or greater in a sample of 12 patients with a two-sided alpha of 0.05 and a power of 0.88. All patients in a cohort will undergo the full 5 ½ weeks of therapy for toxicity assessment. NCI Common Toxicity Criteria version 4.0 will be used to grade toxicity.
|Study Start Date:||December 2006|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (triapine, radiation therapy)
Patients undergo radiotherapy once daily, 5 days a week, for approximately 5.5 weeks (a total of 28 fractions). Patients also receive 3-AP (Triapine) IV over 2 hours 3 days a week every other week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine) until the maximum tolerated dose (MTD) is determined.
Other Names:Radiation: 3-Dimensional Conformal Radiation Therapy
I. To determine the maximal tolerable dose (MTD) of 3-AP administered in combination with radiation therapy (XRT) in patients with locally advanced pancreatic carcinomas.
I. To document the therapeutic response of this combination in patients with locally advanced pancreatic carcinomas.
II. To establish radiographic correlates using secretin stimulated magnetic resonance cholangiopancreatography (MRCP) and dynamic contrast enhanced magnetic resonance imaging (MRI).
III. To measure deoxycytidine triphosphate (dCTP) levels in peripheral blood mononuclear cells (PBMCs)before and after treatment at specified times and try to correlate findings to activity and toxicity of triapine.
OUTLINE: This is a dose-escalation study of 3-AP (Triapine®). Patients undergo radiotherapy once daily, 5 days a week, for approximately 5½ weeks (a total of 28 fractions).
Patients also receive 3-AP (Triapine®) IV over 2 hours 3 days a week every other week for 5½ weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. After completion of study treatment, patients are followed monthly for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00288093
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Tanios Bekaii-Saab||Ohio State University|