RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Gadolinium texaphyrin may increase the effectiveness of radiation therapy by making tumor cells more sensitive to treatment. PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus gadolinium texaphyrin in treating patients with bile duct, gallbladder, or pancreatic cancer that cannot be removed surgically.

Condition	Treatment or Intervention	Phase
stage III pancreatic cancer stage IVB pancreatic cancer stage II pancreatic cancer unresectable gallbladder cancer unresectable extrahepatic bile duct cancer stage IVA pancreatic cancer	Drug: motexafin gadolinium	Phase I

Further Study Details: 

OBJECTIVES: I. Define the safety and toxicity of gadolinium texaphyrin (Gd-Tex) when given concurrently with radiation therapy (RT) 3 times weekly for 16 doses, in patients with locally advanced unresectable pancreatic and biliary tree tumors. II. Evaluate the pharmacokinetics of this treatment on this schedule in these patients. III. Assess tumor uptake of Gd-Tex in these patients. IV. Determine a maximum tolerated dose of Gd-Tex in these patients. V. Evaluate the objective response to Gd-Tex administration with RT in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of gadolinium texaphyrin (Gd-Tex). Patients receive IV Gd-Tex 3 times weekly by IV injection over 15 minutes with concurrent external beam radiation therapy (RT) over 5.5 weeks (total of 16 doses; RT is delivered 5 days a week for a total of 28 fractions). In the absence of dose limiting toxicity (DLT) in the first cohort of 3 patients treated, subsequent cohorts each receive escalating doses on the same schedule. If DLT is observed in 2 of 3 patients or 2 of 6 patients at a given dose level, then dose escalation ceases and that dose is declared the maximum tolerated dose (MTD), and the next lower dose is declared the recommended dose for phase II studies. Patient1s are followed at 4 weeks after the end of RT.

PROJECTED ACCRUAL: Approximately 28-31 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed locally advanced, unresectable carcinoma of the biliary tree or pancreas
• Metastatic disease allowed on a case by case basis provided the following criteria exists:
• Minimal or low volume disease; Need for palliative radiotherapy to primary tumor with or without gadolinium texaphyrin; Systemic therapy no longer required
• Measurable disease in at least 2 dimensions

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to primary site of tumor
• Surgery: At least 3 weeks since major surgery
• Other: At least 4 weeks since other prior investigational drugs; No other concurrent investigational drugs

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; No history of G6PD deficiency
• Hepatic: Bilirubin no greater than 2.0 mg/dL; AST and ALT no greater than 1.5 times upper limit of normal
• Renal: Creatinine less than 1.6 mg/dL
• Other: Not pregnant or nursing; Effective contraception required of fertile patients; No history of porphyria; No active infection; No ascites requiring therapy

New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
Pennsylvania
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States

Study chairs or principal investigators

Ramesh K. Ramanathan,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000066423; PCI-97-108; NCI-T97-0109
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003411
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08