Clinical trial NCT00276744
Conditions: Pancreatic Cancer
Keywords: recurrent pancreatic cancer stage III pancreatic cancer adenocarcinoma of the pancreas stage I pancreatic cancer stage II pancreatic cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2005-10-01; Completion date: 2010-04-01
Enrollment: 249 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Treating tumor tissue in the laboratory with different drugs may help doctors find the best drug for treating individual patients with pancreatic cancer.

PURPOSE: This phase II trial is studying an individualized drug treatment selection process, based on laboratory results, for treating patients with pancreatic cancer that can be removed by surgery.

Detailed description:
OBJECTIVES:

* Establish tumor xenografts from patients with resectable adenocarcinoma of the pancreas who undergo surgical resection at Johns Hopkins Hospital.
* Determine the activity of a series of 10 anticancer drugs against these tumors in ex vivo studies.
* Determine the response rate, time to treatment failure, and 6-month survival rate in patients whose tumors were xenografted and treated in the mouse when treated with the most active agent identified in that model.
* Define determinants of susceptibility and resistance to the drugs in xenografted tumors.

OUTLINE:

* Part I (surgical resection, tumor xenografts generation, and drug selection): Patients undergo surgical resection. The resected tumor tissue is implanted in laboratory mice to generate tumor xenografts. The mice are then treated with a series of 10 approved anticancer drugs, whose anticancer activity are ranked from the most to the least effective based on response of the tumor xenografts. The most effective drug is identified for the individual patient. Patients for whom no drug is found to be effective are removed from the study. Patients who develop progressive disease after surgical resection and after mice data is available proceed to part II.
* Part II (individual patient treatment): Patients receive the most effective drug identified in part I in the absence of disease progression or unacceptable toxicity. The drugs may include bortezomib, capecitabine, cetuximab, docetaxel, erlotinib hydrochloride, gemcitabine hydrochloride, irinotecan hydrochloride, mitomycin C, sirolimus, or thalidomide.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Arms: arm 1: PART A: Participants will have their tumors collected at the time of conventional surgery. Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Patients will then proceed to receive adjuvant treatment based on physician discretion and will be followed until disease progression.

Capecitabine 1,5 mmol/kg Oral gavage 1- 5 days x 2 weeks Cetuximab 500 mg IP Twice a week x 2 weeks Docetaxel 20 mg/kg IV Once at week x 4 weeks Erlotinib 75 mg/kg IP 1-5 days x 2 weeks Gemcitabine 100 mg/kg IP Twice a week x 4 weeks Irinotecan 50 mg/kg IV Twice a week Mitomycin C 5 mg/kg IP One dose Rapamycin 4 mg/kg IP 1-5 days x 2 weeks

PART B: At the time of progression, patients will be evaluated for Part B of the study and treated with the drug selected in Part A as the most active using approved doses and schedules of administration.
Interventions: intervention 1: cetuximab intervention 2: capecitabine intervention 3: docetaxel intervention 4: Erlotinib intervention 5: Gemcitabine intervention 6: Irinotecan intervention 7: mitomycin C intervention 8: rapamycin intervention 9: conventional surgery
Intervention descriptions: intervention 1: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 2: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 3: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 4: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 5: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 6: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 7: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 8: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs. intervention 9: Tumors will be implanted in nude mice and treated with a set of 8 commercially available anticancer drugs. Drugs will be ranked based in their activity from most to least active. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs.

Protocol documents: