Tissue Pharmacokinetics of Intraoperative Gemcitabine in Resectable Adenocarcinoma of the Pancreas

NCT01276613 | Terminated Early Phase 1 FDA Drug

• 4 other identifiers: 2010-0371NCI-2011-00244RSD1429)WS#23
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if gemcitabine can enter pancreas cancer cells, to measure the amount of it that may enter the cells, and for biomarker testing. Biomarkers may be related to participant's reaction to the study drug.

Conditions

Pancreatic Cancer

Keywords

Resectable Adenocarcinoma of the Pancreas; Gemcitabine; Gemcitabine Hydrochloride; Gemzar

Outcome Measures

Primary Outcomes (2)

• Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue

  Pharmacokinetic (PK) Testing of up to 10 blood samples (about 1 tablespoon each time) drawn during surgery starting before gemcitabine infusion and at end of surgery. Blood samples used to measure levels of gemcitabine in blood at the different time points.

  Collection during surgery, participants followed 30 days post surgery

• Gemcitabine DNA Levels in Human Pancreatic Cancer Tissue

  CT scans analyzed, mapping 3 to 4 areas of pancreatic tumor based on differential enhancement patterns within the tumors, where each selected region is uniform within 5-10 HU at each phase of the CT. Each region will comprise no more than 33% of the greatest size of the tumor. Model parameters for each region plugged into the predictive equations for YVmax, YTmax, R0, and AUC.

  Before surgery, participants followed 30 days post surgery

Secondary Outcomes (1)

• Effect of Losartan on Gemcitabine DNA Incorporation Human Pancreatic Cancer Tissue

  Before surgery, participants followed 30 days post surgery

Study Arms (2)

Intraoperative Gemcitabine

EXPERIMENTAL

Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min. Drug infusion started 100 minutes prior to complete gross tumor removal in order to have drug administration complete at tumor removal.

Drug: Gemcitabine

Intraoperative Gemcitabine + Losartan

EXPERIMENTAL

Losartan 50 mg by mouth daily for one week and 50 to 100 mg of Losartan by mouth daily for at least 1 week and at most 3 weeks prior to surgical resection. Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min. Drug infusion started 100 minutes prior to complete gross tumor removal in order to have drug administration complete at tumor removal.

Drug: Gemcitabine; Drug: Losartan

Interventions

Gemcitabine DRUG

Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min.

Also known as: Gemcitabine Hydrochloride, Gemzar

Intraoperative Gemcitabine; Intraoperative Gemcitabine + Losartan

Losartan DRUG

50 mg by mouth daily for one week and 50 to 100 mg of Losartan by mouth daily for at least 1 week and at most 3 weeks prior to surgical resection.

Intraoperative Gemcitabine + Losartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologic or histologic proof of adenocarcinoma of the pancreas is required. Patients with Islet cell tumors are not eligible.
• Patients do not have known metastases.
• Patients must have potentially resectable pancreatic cancer and have agreed to undergo surgical resection at M D Anderson Cancer Center. They will have undergone staging (physical examination, chest x-ray, contrast enhanced CT or MRI (if CT contraindicated) and/or angiogram to determine resectability. Potentially resectable is defined as:No extra-pancreatic disease; No evidence (on CT/MRI) of tumor extension to the celiac axis or SMA; No evidence (CT/MRI or angiogram) of occlusion of the SMV or SMPV confluence.
• Patients with a Karnofsky performance status greater than 70 are eligible.
• There will be no upper age restriction. Patients less than 18 years of age are excluded from the protocol because adenocarcinoma of the pancreas is rarely seen in the pediatric population.
• Adequate renal, and bone marrow function: Leukocytes \>= 3,000/uL; Absolute neutrophil count \>= 1,500/uL; Platelets \>= 100,000/Ul; Serum creatinine \<= 2.0 mg/dL.
• Adequate Hepatic function (endoscopic or percutaneous drainage as needed): Total bilirubin \< = 3 X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) \<= 5 X institutional ULN.
• Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude administration of gemcitabine. Patients with uncontrolled congestive heart failure, unstable angina and myocardial infarction within 3 months will be excluded.
• Patient is not pregnant. Women of childbearing potential (defined as those who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must agree to practice adequate contraception and to refrain from breast-feeding, as specified in the informed consent.
• Patients must sign a study-specific consent form.

You may not qualify if:

• Patient has received preoperative chemotherapy and/or radiation.
• Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia.
• Identification of metastatic disease.
• Inability to comply with study and/or follow-up procedures.
• Patients \< 18 years of age.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Koay EJ, Truty MJ, Cristini V, Thomas RM, Chen R, Chatterjee D, Kang Y, Bhosale PR, Tamm EP, Crane CH, Javle M, Katz MH, Gottumukkala VN, Rozner MA, Shen H, Lee JE, Wang H, Chen Y, Plunkett W, Abbruzzese JL, Wolff RA, Varadhachary GR, Ferrari M, Fleming JB. Transport properties of pancreatic cancer describe gemcitabine delivery and response. J Clin Invest. 2014 Apr;124(4):1525-36. doi: 10.1172/JCI73455. Epub 2014 Mar 10.

  PMID: 24614108 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Losartan

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Tetrazoles

Study Officials

• Michael Kim, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: January 1, 2011
• Primary Completion: April 19, 2019
• Study Completion: April 19, 2019
• Last Updated: May 2, 2019

Record last verified: 2019-04

Locations

US (1)