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Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01938716
Recruitment Status : Terminated (Early termination due to low accrual)
First Posted : September 10, 2013
Results First Posted : November 5, 2020
Last Update Posted : November 5, 2020
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if gemcitabine given during surgery can enter pancreas cancer cells in patients who have already received chemotherapy and radiation.

Gemcitabine is a drug used to treat pancreatic cancer. However, it has not previously been studied if gemcitabine can enter pancreatic cancer cells. Gemcitabine is designed to block the growth of cancer cells, which may cause cancer cells to die.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Gemcitabine Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Tissue Pharmacokinetics of Intraoperative Gemcitabine in Adenocarcinoma of the Pancreas After Preoperative Chemoradiation Therapy
Actual Study Start Date : March 2012
Actual Primary Completion Date : June 3, 2019
Actual Study Completion Date : June 3, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gemcitabine Infusion
Gemcitabine administered intravenously as a dose of 500 mg/m2 at a fixed dose rate of 10 mg/m2/min for the first 5 patients (to validate hematologic safety). Next 15 subsequent patients receive 750 mg/m2 at a fixed dose rate of 10 mg/m2/min. The drug infusion started 50-75 minutes prior to complete gross tumor removal (timing dependent on dose) in order to have drug administration complete at tumor removal.
Drug: Gemcitabine
500 mg/m2 at a fixed dose rate of 10 mg/m2/min by vein for the first 5 patients during pancreatic surgery. Next 15 subsequent patients receive 750 mg/m2 by vein at a fixed dose rate of 10 mg/m2/min.
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

Primary Outcome Measures :
  1. To Quantifiably Assess Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue After a Single Intraoperative Infusion in Patients. [ Time Frame: through study completion, up to 2 years and 6 months ]
    The quantification of serum, PBMC, and cancer tissue levels of gemcitabine from frozen samples will be assessed using standardized techniques in high performance liquid chromatography-mass spectometry (HPLC/MS).

Secondary Outcome Measures :
  1. To Measure Intra-DNA Gemcitabine (dFdC) Levels Using a Novel Assay Liquid Chromatography-mass Spectometry (LC/MS/MS). [ Time Frame: through study completion, up to 2 years and 6 months ]
    Gemcitabine incorporation in DNA will be quantified by a proprietary LC/MS/MS method developed by Eli Lilly and performed by Advion BioServices. DNA extracted from the tissue samples to be sent to Advion.

  2. To Assess and Validate Previously Described Markers That May be Predictive of Gemcitabine Sensitivity or Resistance. [ Time Frame: through study completion, up to 2 years and 6 months ]
    The mRNA level is measured using real time PCR and protein expressed by IHC, Gene expression level will be correlated to the gemcitabine measurements. Additionally measure markers of proliferation and apoptosis by p21and ki67 IHC and fluorescent TUNEL analysis.

  3. To Measure the Impact of Microvessel Density and the Molecular Expression Level of the Hh Signaling Pathway on Gemcitabine Delivery and DNA Incorporation. [ Time Frame: through study completion, up to 2 years and 6 months ]
    The mRNA and protein expression of SHH, Gli, and SMO will be measured by RT-PCR and IHC method, respectively.

  4. To Correlate Intratumoral Gemcitabine Levels and Its Tumoricidal Activity With Ki67 Index and Intratumoral Apoptosis. [ Time Frame: through study completion, up to 2 years and 6 months ]
    Measure markers of of proliferation and apoptosis by p21 and ki67 IHC and fluorescent TUNEL analysis.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Cytologic or histologic proof of adenocarcinoma of the pancreas is required. Patients with Islet cell tumors are not eligible.
  2. Patients do not have known metastases.
  3. Patients must have potentially resectable or borderline resectable pancreatic cancer and have agreed to undergo surgical resection at MD Anderson Cancer Center if operable. They will have undergone staging (physical examination, chest x-ray, contrast enhanced CT or MRI (if CT contraindicated) and/or angiogram) to determine resectability.
  4. Patients have completed radiation and chemotherapy with either fluoropyrimidines (5-FU or capecitabine) or gemcitabine as a radiosensitizing agent as part of their preoperative therapy. Previous systemic chemotherapy alone is not allowed. Preoperative therapy will be completed at least 4 weeks prior to surgery.
  5. Patients with Karnofsky performance status > 70 are eligible.
  6. 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.
  7. 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; Creatinine clearance >= 60 ml/min (calculated by the Cockcroft -Gault equation)
  8. 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
  9. 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.
  10. Patient is not pregnant. Women of childbearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) and refrain from breast-feeding, as specified in the informed consent.
  11. Patients must sign a study-specific consent form.

Exclusion Criteria:

  1. Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia (NYHA [New York Heart Association] Class III and IV).
  2. Identification of metastatic disease.
  3. Patients with a known hypersensitivity to Gemcitabine.
  4. Pregnant women
  5. Inability to comply with study and/or follow-up procedures.
  6. Patients < 18 years of age.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01938716

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Gauri Varadhachary, MD, MBBS M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01938716    
Other Study ID Numbers: 2011-0703
NCI-2013-02211 ( Registry Identifier: NCI CTRP )
First Posted: September 10, 2013    Key Record Dates
Results First Posted: November 5, 2020
Last Update Posted: November 5, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Pancreatic Cancer
Adenocarcinoma of the Pancreas
Intratumoral gemcitabine levels
Pancreatic surgery
Pharmacokinetic testing
Gemcitabine Hydrochloride
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs