Clinical trial NCT00288093: 3-AP and Radiation Therapy in Treating Patients With Stage III Pancreatic Cancer That Cannot Be Removed By Surgery
Official title: A Phase I Study of Triapine® in Combination With Radiation Therapy in Locally Advanced Pancreas Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Stage III Pancreatic Cancer AJCC v6 and v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-02-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas

  * Unresectable nonmetastatic (stage III) disease
* ECOG performance status 0-2
* Life expectancy \> 12 weeks
* WBC ≥ 3,000/mm\^3
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 2 times upper limit of normal (ULN)
* AST/ALT ≤ 3 times ULN
* Creatinine normal ORcreatinine clearance ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception prior to and during study treatment
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to 3-AP (Triapine®) or other agents used in study
* No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
* No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would complicate compliance with study treatment
* No pulmonary disease (i.e., dyspnea at rest, requiring supplemental oxygen, or baseline oxygen saturation \< 92%)
* No prior chemotherapy or radiotherapy
* No concurrent antiretroviral therapy for HIV-positive patients
* No other concurrent investigational agents
* No other concurrent anticancer agents or therapies

Primary outcomes:
measure: MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
timeFrame: Observed clinically for 3-4 hours after each 3-AP infusion during the first week of treatment
Secondary outcomes:
measure: Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP
timeFrame: Immediately before and after 3-AP on the first and last day of treatment
measure: Radiographic correlates using secretin-stimulated MRCP and dynamic contrast enhanced MRI
timeFrame: Prior to treatment (baseline), 2 weeks within and 4 weeks after combined-modality therapy
measure: Therapeutic response as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: 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.
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Tanios Bekaii-Saab
role: PRINCIPAL_INVESTIGATOR
References: