Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy

NCT01938716 | Terminated Results FDA Drug

• 2 other identifiers: 2011-0703NCI-2013-02211
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer; Adenocarcinoma of the Pancreas; Intratumoral gemcitabine levels; Pancreatic surgery; Pharmacokinetic testing; PK; Gemcitabine; Gemcitabine Hydrochloride; Gemzar

Outcome Measures

Primary Outcomes (1)

• To Quantifiably Assess Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue After a Single Intraoperative Infusion in Patients.

  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).

  through study completion, up to 2 years and 6 months

Secondary Outcomes (4)

• To Measure Intra-DNA Gemcitabine (dFdC) Levels Using a Novel Assay Liquid Chromatography-mass Spectometry (LC/MS/MS).

  through study completion, up to 2 years and 6 months

• To Assess and Validate Previously Described Markers That May be Predictive of Gemcitabine Sensitivity or Resistance.

  through study completion, up to 2 years and 6 months

• To Measure the Impact of Microvessel Density and the Molecular Expression Level of the Hh Signaling Pathway on Gemcitabine Delivery and DNA Incorporation.

  through study completion, up to 2 years and 6 months

• To Correlate Intratumoral Gemcitabine Levels and Its Tumoricidal Activity With Ki67 Index and Intratumoral Apoptosis.

  through study completion, up to 2 years and 6 months

Study Arms (1)

Gemcitabine Infusion

EXPERIMENTAL

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

Interventions

Gemcitabine DRUG

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.

Also known as: Gemcitabine Hydrochloride, Gemzar

Gemcitabine Infusion

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 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.
• 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.
• Patients with Karnofsky performance status \> 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; Creatinine clearance \>= 60 ml/min (calculated by the Cockcroft -Gault equation)
• 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 (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.
• Patients must sign a study-specific consent form.

You may not qualify if:

• Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia (NYHA \[New York Heart Association\] Class III and IV).
• Identification of metastatic disease.
• Patients with a known hypersensitivity to Gemcitabine.
• Pregnant women
• 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 Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

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

Results Point of Contact

• Title: Dr. Gauri R Varadhachary,Professor, GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

gvaradha@mdanderson.org

713-792-2828

Study Officials

• Gauri Varadhachary, MD, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: March 1, 2012
• Primary Completion: June 3, 2019
• Study Completion: June 3, 2019
• Last Updated: November 5, 2020
• Results First Posted: November 5, 2020

Record last verified: 2020-10

Locations

US (1)