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Tissue Pharmacokinetics of Intraoperative Gemcitabine in Resectable Adenocarcinoma of the Pancreas

30 april 2019 bijgewerkt door: M.D. Anderson Cancer Center
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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

The Study Drugs:

Gemcitabine is a drug used to treat pancreatic cancer. However, there are no studies that show that gemcitabine is able to enter pancreatic cancer cells.

Losartan is a drug that lowers blood pressure. It also may increase the amount of gemcitabine that reaches the cancer cells. Participant may be asked to take this drug before participant's surgery.

Before Surgery:

If participant is found to be eligible and participant agrees to take part in this study, the following tests will be done before participant's surgery:

  • Participant will have a routine CT (computed tomography) scan and a research MRI (magnetic resonance imaging) of participant's abdomen to check the status of the disease.
  • Blood (about 3-4 teaspoons) will be drawn for biomarker testing.

Participant may be asked to take losartan for 2-4 two to four weeks before participant's surgery (described below).

Surgery:

Participant's surgery will be performed in the same way as it would be even if participant was not taking part in this study. Participant will sign a separate consent form for surgery. The length of the surgery and the time participant is under anesthesia are not changed by taking part in the study.

To measure how much gemcitabine enters pancreas cancer cells, participants who are having their pancreatic cancer removed by surgery will receive an infusion of gemcitabine during the surgery. Some of the pancreatic cancer tissue removed then will be checked to learn if gemcitabine is found in the cancer cells.

During surgery, participant will have routine procedures to learn if the disease has spread to other areas. If the disease has spread beyond the pancreas, surgical removal is not possible.

If for any reason during the surgery, the surgeon decides that removal of the pancreas is not possible, participant will not receive gemcitabine and participation in this study will end.

If there are no signs of spread or other reasons the cancer cannot be removed, the surgeon will begin the process of removal of the disease.

Gemcitabine Infusion:

Participant will receive an infusion of gemcitabine just before the surgeon begins to remove the cancer. Gemcitabine will be given through an infusion catheter that is placed in the operating room after participant is asleep. The infusion will take over 100 minutes. The infusion catheter is not required for the study but is a standard of care procedure for all participants who are having pancreatic cancer surgery. Participant will sign a separate consent form for the infusion catheter.

Losartan Administration:

If participant is asked to take losartan, participant will take 1 tablet by mouth every day for up to 4 weeks before participant's surgery. After Week 1, the study staff will tell participant if participant's dose will stay the same or increase, based on any side effects that participant may have.

Blood and Tissue Collection:

Up to 10 blood samples (about 1 tablespoon each time) will be drawn during surgery starting before the gemcitabine infusion begins and at the end of surgery. The blood samples are used to measure the levels of gemcitabine in participant's blood at different time points. This is called pharmacokinetic (PK) testing. The blood will also be used for biomarker testing. Biomarkers are chemical "markers" in the blood/tissue that may be related to participant's reaction to the study drug.

Some of the tumor tissue and normal tissue removed during surgery will be collected to learn if gemcitabine is able to enter the tissue cells and for biomarker testing.

Length of Study:

Participant's active participation in this study will be over once participant has had surgery and completed the follow-up. The research team will continue to collect information on participant for 30 days after surgery (or until participant is no longer having side effects).

Follow-Up:

The study team will follow participant's health status for 30 days after surgery to check if participant is having any side effects from gemcitabine. This follow-up will be done daily while participant is in the hospital recovering from the surgery. Follow-up will also occur at the time of a routine clinic visit, or by phone call at least once weekly. These calls should last about 5 minutes each.

This is an investigational study. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic cancer. Its use during surgery is investigational.

Losartan is FDA approved and commercially available for the treatment of high blood pressure and diabetic nephropathy. It is not approved for the treatment of pancreatic cancer.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

18

Fase

  • Vroege fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • University of Texas MD Anderson Cancer Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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 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.
  4. Patients with a Karnofsky performance status greater than 70 are eligible.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Patients must sign a study-specific consent form.

Exclusion Criteria:

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Intraoperative Gemcitabine
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.
Geneesmiddel: Gemcitabine
Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min.
Andere namen:
  • Gemzar
  • Gemcitabinehydrochloride
Experimenteel: Intraoperative Gemcitabine + Losartan

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.
Geneesmiddel: Gemcitabine
Gemcitabine administered by the anesthesiologist as a dose of 1,000mg/m2 at a fixed dose rate of 10mg/m2/min.
Andere namen:
  • Gemzar
  • Gemcitabinehydrochloride
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue
Tijdsspanne: Collection during surgery, participants followed 30 days post surgery
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
Tijdsspanne: Before surgery, participants followed 30 days post surgery
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Effect of Losartan on Gemcitabine DNA Incorporation Human Pancreatic Cancer Tissue
Tijdsspanne: Before surgery, participants followed 30 days post surgery
Root mean square error estimated of prediction from the pre-therapy CT scan to be 0.14 pg dFdC/ng dG. From this estimate of the error of prediction, 80% power calculated to detect an absolute increase in gemcitabine delivery of 0.36 pg dFdC/ng dG and a 90% power to detect an absolute increase in gemcitabine delivery of 0.42 pg dFdC/ng dG in a given participant.
Before surgery, participants followed 30 days post surgery

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

M.D. Anderson Cancer Center

Onderzoekers

  • Hoofdonderzoeker: Michael Kim, MD, M.D. Anderson Cancer Center

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 januari 2011

Primaire voltooiing (Werkelijk)

19 april 2019

Studie voltooiing (Werkelijk)

19 april 2019

Studieregistratiedata

Eerst ingediend

12 januari 2011

Eerst ingediend dat voldeed aan de QC-criteria

12 januari 2011

Eerst geplaatst (Schatting)

13 januari 2011

Updates van studierecords

Laatste update geplaatst (Werkelijk)

2 mei 2019

Laatste update ingediend die voldeed aan QC-criteria

30 april 2019

Laatst geverifieerd

1 april 2019

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2010-0371
  • NCI-2011-00244 (Register-ID: NCI CTRP)
  • RSD1429) (Ander subsidie-/financieringsnummer: RSNA)
  • WS#23 (Ander subsidie-/financieringsnummer: GE)

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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