Individualized Drug Treatment for Treating Patients With Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT00276744
• Recruitment Status: Terminated
• First Posted: January 13, 2006
• Results First Posted: August 27, 2018
• Last Update Posted: October 24, 2018
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: January 12, 2006
• First Posted Date: January 13, 2006
• Results First Submitted Date: February 27, 2018
• Results First Posted Date: August 27, 2018
• Last Update Posted Date: October 24, 2018
• Study Start Date: October 2005
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2018)

6-month Overall Survival [ Time Frame: 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

• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00276744 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Individualized Drug Treatment for Treating Patients With Pancreatic Cancer
• Official Title: A Feasibility Study for Individualized Treatment of Patients With Advanced 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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.

Study Arms

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.

Interventions:

• Biological: cetuximab
• Drug: capecitabine
• Drug: docetaxel
• Drug: Erlotinib
• Drug: Gemcitabine
• Drug: Irinotecan
• Drug: mitomycin C
• Drug: rapamycin
• Procedure: conventional surgery

• Publications *: Villarroel MC, Rajeshkumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, Hruban RH, Eshleman JR, Klein A, Laheru D, Donehower R, Hidalgo M. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol Cancer Ther. 2011 Jan;10(1):3-8. doi: 10.1158/1535-7163.MCT-10-0893. Epub 2010 Dec 6.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 27, 2018): 249
• Original Enrollment: Not Provided
• Actual Study Completion Date: April 2010
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00276744
• Other Study ID Numbers: J0507; P30CA006973 ( U.S. NIH Grant/Contract ); CDR0000455000; 05-04-14-02 ( Other Identifier: JHM IRB )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Daniel A. Laheru, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: October 2018