3-AP and Radiation Therapy in Treating Patients With Stage III Pancreatic Cancer That Cannot Be Removed By Surgery

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Pancreatic Adenocarcinoma; Stage III Pancreatic Cancer AJCC v6 and v7

Treatments: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Triapine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00288093

NCI-2009-00120 (Registry Identifier)

7044 (Other Identifier)

U01CA076576 (U.S. NIH Grant/Contract)

CSU-05011

CDR0000455065

05011

OSU-2005C0030

NCI-7044

P30CA016058 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Treatment (triapine, radiation therapy)

Experimental group

Description:

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.

Treatment:

Drug: Triapine

Radiation: 3-Dimensional Conformal Radiation Therapy