Pancreatic Cancer
Conditions
Keywords
recurrent pancreatic cancer, stage III pancreatic cancer, adenocarcinoma of the pancreas, stage I pancreatic cancer, stage II pancreatic cancer
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.
Interventions
BIOLOGICALcetuximab
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.
DRUGcapecitabine
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.
DRUGdocetaxel
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.
DRUGErlotinib
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.
DRUGGemcitabine
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.
DRUGIrinotecan
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.
DRUGmitomycin 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.
DRUGrapamycin
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.
PROCEDUREconventional 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.
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
Part A Inclusion Criteria 1. Suspected adenocarcinoma of the pancreas with resectable disease schedule to have surgical resection at the Johns Hopkins Hospital. 2. Age ≥ 18 years old. 3. Ability to understand and willingness to sign a written informed consent document. Part B Inclusion Criteria 1. Participation in Part A of the study with informative mouse xenograft data. 2. 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. 3. ECOG performance status 0 or 1 4. Age ≥ 18 years old. 5. Expected survival \> 12 weeks. 6. No prior treatment for recurrent disease. 7. 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. 8. 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
1. Patients in whom histologic or cytologic diagnosis is not consistent with adenocarcinoma. 2. 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 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Overall Survival | 6 months | Percentage of patients survived at 6 months for patients whose tumors were xenografted and treated in the mouse when treated with the most active agent identified in that model |
Countries
United States
Participant flow
Pre-assignment details
249 participants were enrolled however 240 received intervention in the study. Reason unknown and data is not accessible for the 9 remaining participants who were not assigned to intervention
Participants by arm
| Arm | Count |
|---|---|
| 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. | 240 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| PART A | Reason unknown | 98 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 53 Participants |
| Age, Categorical Between 18 and 65 years | 187 Participants |
| Region of Enrollment United States | 240 participants |
| Sex: Female, Male Female | 115 Participants |
| Sex: Female, Male Male | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
6-month Overall Survival
Percentage of patients survived at 6 months for patients whose tumors were xenografted and treated in the mouse when treated with the most active agent identified in that model
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | 6-month Overall Survival | 53 percentage of participants |