Gemcitabine With or Without Capecitabine and/or Radiation Therapy or Gemcitabine With or Without Erlotinib in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT00634725
First received: March 12, 2008
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known which regimen of chemotherapy with or without erlotinib and/or radiation therapy is most effective in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying giving gemcitabine together with or without capecitabine and/or radiation therapy to see how well it works compared with giving gemcitabine together with or without erlotinib in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.


Condition Intervention Phase
Pancreatic Cancer
Drug: capecitabine
Drug: erlotinib hydrochloride
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Multicenter Phase III Study in Patients With Locally Advanced Adenocarcinoma of the Pancreas: Gemcitabine With or Without Chemoradiotherapy and With or Without Erlotinib. Intergroup Study

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • Overall survival [ Time Frame: from the date of the first randomization to the date of patient death,due to any cause, or to the last date the patient was known to be alive, assessed up to 8 years after the beginning of the study ] [ Designated as safety issue: No ]
    an interim analysis is planned when 196 deaths will be observed


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: time from the date of the first randomization to the date of progressive disease or death, assessed up to 8 years after the beginning of the study. ] [ Designated as safety issue: No ]
  • Relationship between biological markers and survival [ Time Frame: From baseline to death, assessed up to 8 years after the beginning of the study ] [ Designated as safety issue: No ]
    1 biopsy/patient of the pancreas before treatment

  • tolerance to erlotinib [ Time Frame: from start of treatment until the event has resolved or stabilized or until death ] [ Designated as safety issue: No ]

    To evaluate tolerance to erlotinib as maintenance treatment after the end of CT or CRT.

    During each visit, any adverse events will be noted and graded according to version 3 of the NCI-CTCAE. Any adverse events that persist at the end of the CTI will be followed up until they disappear.



Estimated Enrollment: 820
Study Start Date: February 2008
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 (A1) - Gemcitabine
Gemcitabine 2 months, then stop until progression
Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis
Experimental: Arm 2 (B1) Gemcitabine + Erlotinib
B1 Gemcitabine + Erlotinib (100mg/d) 2 months, then erlotinib maintenance (150 mg/d)until progression
Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis
Experimental: Arm 3 (A2) CRT
A2 CRT then stop until progression
Drug: capecitabine Other: laboratory biomarker analysis Radiation: radiation therapy
Experimental: Arm 4 (B2) CRT then erlotinib
B2 CRT then erlotinib maintenance (150mg/d) until progression
Drug: capecitabine Drug: erlotinib hydrochloride Other: laboratory biomarker analysis Radiation: radiation therapy

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • To assess whether administrating chemoradiotherapy in patients whose tumor is controlled after 4 months of induction chemotherapy (CT) increases survival compared with continuation of the same CT in patients with unresectable, locally advanced adenocarcinoma of the pancreas.

Secondary

  • To assess whether erlotinib hydrochloride combined with gemcitabine hydrochloride and administered as maintenance treatment increases progression-free survival compared with gemcitabine hydrochloride alone and without maintenance treatment.
  • To evaluate the response rate in the CT and chemoradiotherapy (CRT) arms.
  • To evaluate tolerance to erlotinib hydrochloride as maintenance treatment after the end of CT or CRT.
  • To study the predictive molecular factors (i.e., survivin, K-ras, EGFR, PTEN, or AKT) of survival.

OUTLINE: This is a multicenter study. Patients in the first randomization are stratified according to center and ECOG performance status (0-1 vs 2). Patients in the second randomization are stratified according to center and initial treatment arm (I vs II).

  • First randomization: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. Following the first evaluation, patients continue to receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99 for a total of 4 months.
    • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. Following the first evaluation, patients continue to receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99. Patients also receive oral erlotinib hydrochloride once daily for 4 months.

After completion of treatment in the first randomization proceed to the second randomization.

  • Second randomization: Patients are randomized to 1 of 4 treatment arms.

    • Arm I: Patients continue gemcitabine hydrochloride as in arm I in the first randomization on days 113, 120, and 127 and on days 141, 148, and 155 for 2 months in the absence of disease progression.
    • Arm II: Patients continue gemcitabine hydrochloride as in arm II in the first randomization on days 113, 120, and 127 and on days 141, 148, and 155 and oral erlotinib hydrochloride daily for 2 months followed by erlotinib hydrochloride alone as maintenance therapy in the absence of disease progression.
    • Arm III: Patients receive oral capecitabine twice daily and undergo radiotherapy beginning on day 127, 5 days a week, for 6 weeks, in the absence of disease progression.
    • Arm IV: Patients receive oral capecitabine twice daily and undergo radiotherapy beginning on day 127, 5 days a week, for 6 weeks. Beginning 15 days after completion of CRT, patients receive a reintroduction of oral erlotinib hydrochloride alone once daily in the absence of disease progression or unacceptable toxicity.

Tumor tissue will be analyzed for the relationship between biological markers and resistance to treatment.

After completion of study treatment, patients are followed every 2 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the pancreas meeting the following criteria:

    • De novo locally advanced disease
    • Unresectable disease
    • Stage III according to the UICC classification

      • No distant metastases
      • No localized stage IA-IIB or metastatic stage IV disease according to UICC classification
    • Not considered for curative resection after pluridisciplinary discussion

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Polynuclear neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

    • For patients who have had a recent biliary drain and whose bilirubin is descending, a value of ≤ 3 times ULN is acceptable
  • Creatinine ≤ 2 mg/dL
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 5 times ULN
  • Albumin ≥ 25 g/L
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of therapy

Exclusion criteria:

  • Diarrhea ≥ grade 2 and/or uncontrolled diarrhea
  • Affiliated with a social security regime
  • Unable to follow instructions for psychological, familial, or geographical reasons
  • Allergic to one of the ingredients in erlotinib hydrochloride
  • Cancer within the past 5 years, except for in situ cancer of the neck of the uterus or basal cell skin cancer
  • Severe infection
  • Ophthalmic disease (i.e., inflammation, keratopathy, or infection)
  • Symptomatic coronary or cardiac insufficiency, myocardial infarction, or stroke within the last 6 months
  • Unable to take oral treatments
  • Gastrointestinal disorders that could be associated with absorption disorders
  • Untreated gastric or duodenal ulcer

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy (including abdominal radiotherapy) or chemotherapy for any reason
  • No prior anti-epidermal growth factor-receptor therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634725

  Show 72 Study Locations
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Investigators
Principal Investigator: Pascal Hammel, MD, PhD Hopital Beaujon
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier: NCT00634725     History of Changes
Other Study ID Numbers: CDR0000589283, GERCOR-LAP-07-D07-1, EU=20827, ROCHE-GERCOR-LAP-07-D07-1, EudraCT- 2007-001174-81
Study First Received: March 12, 2008
Last Updated: November 8, 2012
Health Authority: France: ANSM - Agence Nationale de sécurité du médicament et des produits de santé (French Competent Authority, previously called AFSSAPS)

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
adenocarcinoma of the pancreas
stage III pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Capecitabine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014