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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00288093
First received: February 6, 2006
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Stage III Pancreatic Cancer
Drug: triapine
Radiation: 3-dimensional conformal radiation therapy
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: December 2006
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: triapine
Other Names:
  • 3-AP
  • OCX-191
Radiation: 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288093

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Tanios Bekaii-Saab Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00288093     History of Changes
Other Study ID Numbers: NCI-2009-00120, NCI-2009-00120, OSU-2005C0030, CSU-05011, CDR0000455065, NCI-7044, 05011, 7044, U01CA076576, P30CA016058
Study First Received: February 6, 2006
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014