Capecitabine and docetaxel and Erlotinib in Pancreatic Cancer - Clinical Trials Registry

Study Overview

Status

Terminated

Conditions

Pancreatic Cancer

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

249

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Maryland
  - Baltimore, Maryland, United States, 21231-2410
    - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Part A

Inclusion Criteria

Suspected adenocarcinoma of the pancreas with resectable disease schedule to have surgical resection at the Johns Hopkins Hospital.
Age ≥ 18 years old.
Ability to understand and willingness to sign a written informed consent document.

Part B

Inclusion Criteria

Participation in Part A of the study with informative mouse xenograft data.
Histologically or cytologically confirmed diagnosis of invasive adenocarcinoma of the pancreas and peripancreatic adenocarcinoma, including distal cholangiocarcinoma, duodenal carcinoma, and ampullary pancreatic not amenable to curative treatment.
ECOG performance status 0 or 1
Age ≥ 18 years old.
Expected survival > 12 weeks.
No prior treatment for recurrent disease.
Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of test article.
Adequate liver, renal and bone marrow functions.

WBC > 3,500 cells/mm3 ANC > 1,500 cells/mm3 Platelets > 100,000 cells/mm3 Hemoglobin ≥ 9 g/dl Serum creatinine 2 mg/dl Bilirubin 2 mg/dL ALT, AST, and alkaline phosphatase 5 times the upper limit of normal

Exclusion criteria

Patients in whom histologic or cytologic diagnosis is not consistent with adenocarcinoma.
Patients in whom histologic or cytologic diagnosis is consistent with non epithelial origin tumors, including adenosquamous, islet cell, cystadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma, sarcoma, lymphoma and melanoma
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4. Patients who have had any previous surgery, excluding minor procedures, dental work, skin biopsy, etc. within 4 weeks of enrollment.

5. Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications when treated with chemotherapy. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.

6. Active infections.

7. History of another neoplasm except for non-metastatic, nonmelanoma skin cancers, < 5 years prior to enrollment.

8. Unable to provide informed consent.

9. Treatment with chemotherapy within 30 days of day 1 treatment.

10. Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy (except alopecia).

11. Pregnant women are excluded from this study because the effects of the chemotherapy agents to be tested on the developing fetus are not known. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MMC, breast feeding should be discontinued if the mother is treated with the drug.

12. Patients must not have documented history of clinically significant cardiovascular disease including myocardial infarction (within 12 months prior to randomization), unstable angina, grade II or greater peripheral vascular disease, uncontrolled congestive heart failure or uncontrolled hypertension (SBP>170, DBP>95).

13. Patients with non informative xenograft data including patients whose tumors do not take in the mice, who progress before mice data is available or whose tumors do not respond to any of the selected agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: cetuximab 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. Drug: capecitabine 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. Other Names: xeloda Drug: docetaxel 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. Other Names: taxotere Drug: Erlotinib 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. Other Names: tarceva Drug: Gemcitabine 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. Other Names: gemzar Drug: Irinotecan 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. Other Names: campto Drug: mitomycin C 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. Other Names: mitomycin Drug: rapamycin 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. Other Names: sirolimus Procedure: 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. Biological studies will be conducted in tumor tissues to better understand the response to tested drugs.

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Biological: cetuximab