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Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

4 oktober 2019 bijgewerkt door: Alliance for Clinical Trials in Oncology

A Phase II Study of Preoperative Gemcitabine and Erlotinib Plus Pancreatectomy and Postoperative Gemcitabine and Erlotinib for Patients With Operable Pancreatic Adenocarcinoma

PURPOSE: This phase II trial is studying how well gemcitabine and erlotinib work when given before and after surgery in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these drugs after surgery may kill any tumor cells that remain after surgery.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This is a single arm, non-randomized phase II study. Eligible, fully registered patients will receive preoperative chemotherapy consisting of gemcitabine plus erlotinib. Preoperative chemotherapy will be followed by exploratory laparotomy and pancreaticoduodenectomy. Patients will then receive postoperative chemotherapy consisting of gemcitabine plus erlotinib. Up to 123 patients will be accrued to this study, with the expectation that 78 patients will remain fully eligible and evaluable for the primary endpoint. The primary and secondary objectives for the study are listed below.

Primary Objective:

To estimate the proportion of patients alive at two years from the date of registration

Secondary Objectives:

  1. To determine the resection rate (defined as the fraction of patients who proceed to planned surgery with removal of primary tumor [R0/R1]) following induction treatment with gemcitabine plus erlotinib
  2. To estimate the time to disease progression/relapse
  3. To evaluate the rate of R0, R1, and R2 resections (defined as per the 6th edition of the AJCC Cancer Staging Manual) in patients treated with preoperative gemcitabine plus erlotinib chemotherapy
  4. To evaluate the toxicity profile of preoperative gemcitabine plus erlotinib and the feasibility of postoperative gemcitabine plus erlotinib
  5. To evaluate response rates to preoperative chemotherapy for patients treated with preoperative gemcitabine and erlotinib
  6. To identify molecular predictors of pancreatic cancer response to gemcitabine combined with erlotinib
  7. To identify genetic profiles of pancreatic adenocarcinoma that may be associated with response to neoadjuvant therapy

After completion of postoperative chemotherapy treatment, patients are followed every 3 months for 2 years and then every 6 months for 2 years.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

123

Fase

  • Fase 2

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
  • Verenigde Staten
    • California
      • La Jolla, California, Verenigde Staten, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, Verenigde Staten, 90027
        • Kaiser Permanente Medical Center - Los Angeles
      • Orange, California, Verenigde Staten, 92868
        • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Connecticut
      • Bridgeport, Connecticut, Verenigde Staten, 06606
        • St. Vincent's Medical Center
    • Florida
      • Lakeland, Florida, Verenigde Staten, 33805
        • Lakeland Regional Cancer Center at Lakeland Regional Medical Center
    • Indiana
      • Indianapolis, Indiana, Verenigde Staten, 46237
        • St. Francis Hospital Cancer Care Services
    • Maryland
      • Baltimore, Maryland, Verenigde Staten, 21229
        • St. Agnes Hospital Cancer Center
      • Baltimore, Maryland, Verenigde Staten, 21215
        • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
    • Mississippi
      • Jackson, Mississippi, Verenigde Staten, 39216
        • University of Mississippi Cancer Clinic
    • Nebraska
      • Omaha, Nebraska, Verenigde Staten, 68114
        • Methodist Estabrook Cancer Center
    • New York
      • New York, New York, Verenigde Staten, 10016
        • NYU Cancer Institute at New York University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Verenigde Staten, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Ohio
      • Dayton, Ohio, Verenigde Staten, 45409
        • David L. Rike Cancer Center at Miami Valley Hospital
      • Dayton, Ohio, Verenigde Staten, 45415
        • Samaritan North Cancer Care Center
      • Dayton, Ohio, Verenigde Staten, 45420
        • CCOP - Dayton
      • Kettering, Ohio, Verenigde Staten, 45429
        • Charles F. Kettering Memorial Hospital
      • Troy, Ohio, Verenigde Staten, 45373-1300
        • UVMC Cancer Care Center at Upper Valley Medical Center
    • Oklahoma
      • Tulsa, Oklahoma, Verenigde Staten, 74136
        • Natalie Warren Bryant Cancer Center at St. Francis Hospital
    • Oregon
      • Portland, Oregon, Verenigde Staten, 97213-2967
        • Providence Cancer Center at Providence Portland Medical Center
    • South Carolina
      • Spartanburg, South Carolina, Verenigde Staten, 29303
        • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Virginia
      • Newport News, Virginia, Verenigde Staten, 23606
        • Surgical Oncology Associates
    • West Virginia
      • Morgantown, West Virginia, Verenigde Staten, 26506
        • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
    • Wisconsin
      • Madison, Wisconsin, Verenigde Staten, 53792-6164
        • University of Wisconsin Paul P. Carbone Comprehensive 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

Eligibility Criteria:

  1. Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process.

    NOTE: Patients with tumors of the pancreatic neck, body or tail are not eligible. Patients with evidence of neuroendocrine tumors, duodenal adenocarcinoma, or ampullary adenocarcinoma are not eligible.

  2. Localized, potentially resectable tumors as defined below. All patients must be staged with a chest X-ray or CT, and abdominal CT (contrast-enhanced, helical thin-cut) or MRI. Radiological resectability is defined by the following criteria on abdominal imaging:

    • No evidence of tumor extension to the celiac axis, hepatic artery, or superior mesenteric artery
    • No evidence of tumor encasement or occlusion of the superior mesenteric vein (SMV) or the SMV/portal vein confluence
    • No evidence of visceral or peritoneal metastases

    NOTE: Patients with borderline resectable or marginally resectable pancreatic cancer are not eligible. Patients must meet all objective imaging criteria outlined above.

  3. ≥ 18 years of age
  4. ECOG/Zubrod performance status of 0 or 1
  5. Baseline weight loss ≤ 15% of premorbid weight

  6. Patient must have adequate hematologic, renal, and hepatic function as defined by:

    • WBC ≥ 2,000 cells/mm³
    • ANC ≥ 1,500 cells/mm³
    • Platelets ≥ 100,000 cells/mm³
    • Serum bilirubin ≤ 2.5 mg/dL
    • Serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of ≥ 50 ml/min (24 hour urine collection)
    • ALT < 2.5 times upper limit of normal (ULN)
    • AST < 2.5 times ULN
    • Albumin ≥ 3.2 g/dl

  7. No history of the following:

    • Prior EGFR targeted therapy or therapy for pancreatic cancer
    • Active infection requiring intravenous antibiotics at the time of registration
  8. Non-pregnant and non-breast feeding. Female participants of child bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic ≥ 12 months to be considered not of childbearing potential. All patients of reproductive potential must agree to use an effective method of birth control while receiving study therapy.
  9. No prior malignancy within 5 years of registration (Exceptions: non-melanoma skin cancer, in-situ cancers)

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: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Neoadjuvant therapy + Surgery + Adjuvant therapy
As part of neoadjuvant therapy, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 29, 36, and 43 and oral erlotinib hydrochloride once daily on days 1-43 in the absence of disease progression or unacceptable toxicity. Within 3-6 weeks after completion of neoadjuvant therapy, patients undergo pancreaticoduodenectomy and patients receive gemcitabine hydrochloride and erlotinib hydrochloride as in neoadjuvant therapy within 5-10 weeks post surgery.
Procedure: therapeutische conventionele chirurgie
Geneesmiddel: erlotinib hydrochloride
oral administration
Geneesmiddel: gemcitabine hydrochloride
Intravenous administration

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Survival at 2 Years
Tijdsspanne: At 2 years post-registration
The primary endpoint of this trial is 2-year overall survival, which will be evaluated as the proportion of treatment successes. A treatment success is defined to be an evaluable patient who is alive at two years from the date of registration.
At 2 years post-registration

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Resection Rate
Tijdsspanne: Up to 4 years postoperative chemotherapy treatment

The resection rate is defined as the fraction of patients that proceed to planned surgery with removal of primary tumor (R0/R1) following neoadjuvant treatment with gemcitabine plus erlotinib.The resection rate will be estimated by the binomial point estimate, i.e. as the number of patients that undergo the planned surgery with removal of the primary tumor following neoadjuvant treatment with gemcitabine plus erlotinib divided by the number of evaluable patients. This quantity will also be estimated with a 95% binomial confidence interval.

Curative resection (R0) is defined as macroscopically and microscopically complete resection (with microscopic surgical margin assessment according to AJCC Staging Principles).

An R1 resection is defined as macroscopically complete tumor removal with any positive microscopic surgical margin (bile duct, pancreatic parenchyma, or SMA margins).
Up to 4 years postoperative chemotherapy treatment
Relapse/Progression-free Survival
Tijdsspanne: At 2 years post-registration
Relapse/progression-free survival is defined as the time from date of registration to the date of documentation of disease recurrence/progression. If a patient dies without documentation of disease recurrence/progression, the patient will be considered to have had disease recurrence/progression at the time of their death unless there is sufficient documented evidence to conclude no recurrence/progression occurred prior to death. If a patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation occurred. If a patient is lost to follow-up, s/he will be censored at the data of last contact. The distribution of disease-free survival will be estimated using the method of Kaplan and Meier.
At 2 years post-registration
Number of Participants Experiencing Grade 3 or Higher Adverse Events as Graded by the NCI's Common Toxicity Criteria for Adverse Events
Tijdsspanne: Up to 4 years postoperative chemotherapy treatment
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. These patterns will be summarized with descriptive statistics. The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.
Up to 4 years postoperative chemotherapy treatment
Response Rate
Tijdsspanne: Up to 4 years postoperative chemotherapy treatment
The response rates to preoperative chemotherapy for patients treated with preoperative gemcitabine and erlotinib and rates of accurate pathologic assessment of the resected tumor specimen according to College of American Pathology guidelines will be estimated with a binomial point estimate and corresponding 95% confidence intervals.
Up to 4 years postoperative chemotherapy treatment

Medewerkers en onderzoekers

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

Sponsor

Alliance for Clinical Trials in Oncology

Medewerkers

National Cancer Institute (NCI)
Astellas Pharma Inc
OSI Pharmaceuticals

Onderzoekers

  • Studie stoel: Peter W.T. Pisters, MD, M.D. Anderson Cancer Center

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 april 2009

Primaire voltooiing (Werkelijk)

1 november 2015

Studie voltooiing (Werkelijk)

15 juni 2019

Studieregistratiedata

Eerst ingediend

12 augustus 2008

Eerst ingediend dat voldeed aan de QC-criteria

12 augustus 2008

Eerst geplaatst (Schatting)

13 augustus 2008

Updates van studierecords

Laatste update geplaatst (Werkelijk)

21 oktober 2019

Laatste update ingediend die voldeed aan QC-criteria

4 oktober 2019

Laatst geverifieerd

1 oktober 2019

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ACOSOG-Z5041
  • U10CA076001 (Subsidie/contract van de Amerikaanse NIH)
  • NCI-2009-00348 (Andere identificatie: NCI Clinical Trial Reporting Office)
  • CDR0000609871 (Register-ID: NCI Physician Data Query)

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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