Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01013649
First received: November 13, 2009
Last updated: June 23, 2014
Last verified: April 2014
  Purpose

This randomized phase II-R/III trial studies gemcitabine hydrochloride with or without erlotinib hydrochloride followed by the same chemotherapy regimen with or without radiation therapy and capecitabine or fluorouracil in treating patients with pancreatic cancer that was removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, capecitabine, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride 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. Giving chemotherapy together with or without erlotinib hydrochloride and/or radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective when given with or without erlotinib hydrochloride and/or radiation therapy in treating pancreatic cancer.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Intraductal Papillary Mucinous Neoplasm of the Pancreas
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Drug: gemcitabine hydrochloride
Drug: erlotinib hydrochloride
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Drug: capecitabine
Drug: fluorouracil
Other: laboratory biomarker analysis
Other: quality-of-life assessment
Phase 2
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: A Phase II-R and a Phase III Trial Evaluating Both *Erlotinib (PH II-R) and Chemoradiation (PH III) as Adjuvant Treatment For Patients With Resected Head of Pancreas Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (Phase II) [ Time Frame: From the date of first randomization (gemcitabine vs. gemcitabine/erlotinib) to the date of death or last follow-up, assessed up to 11 years ] [ Designated as safety issue: No ]
    Overall survival will be estimated by the Kaplan-Meier method. The distribution of overall survival estimates between the two arms for both primary endpoint questions will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with overall survival.

  • Overall survival (Phase III) [ Time Frame: From the date of second randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up, assessed up to 11 years ] [ Designated as safety issue: No ]
    Overall survival will be estimated by the Kaplan-Meier method. The distribution of overall survival estimates between the two arms for both primary endpoint questions will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with overall survival.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Disease-free survival will be estimated by the Kaplan-Meier method.

  • Incidence of adverse events assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 11 years ] [ Designated as safety issue: Yes ]
  • Frequency of objective criteria of resectability as measured by preoperative imaging [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  • Changes in fatigue as measured by the FACIT-F (primary) and the PROMIS derived short form (exploratory) [ Time Frame: Baseline up to 24 months ] [ Designated as safety issue: No ]
    The primary HRQoL hypothesis will be tested using the log-rank statistic with a significance level of 0.05. Additionally, analyses of fatigue effect will be performed using the Cox proportional hazard model.


Estimated Enrollment: 950
Study Start Date: November 2009
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (gemcitabine hydrochloride)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (gemcitabine hydrochloride, erlotinib hydrochloride)
Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm III (chemotherapy)
Patients receive 1 course of the same treatment that they receive in arm I or II.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm IV (chemotherapy, chemoradiotherapy)
Patients receive 1 course of the same treatment that they receive in arm I or II. Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy (3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO BID 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Radiation: 3-dimensional conformal radiation therapy
Undergo 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: intensity-modulated radiation therapy
Undergo intensity-modulated radiation therapy
Other Name: IMRT
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologic proof of primary head of pancreas invasive adenocarcinoma managed with a potentially curative resection (i.e., removal of all gross tumor) involving a classic pancreaticoduodenectomy (Whipple) or a pylorus preserving pancreaticoduodenectomy; patients with invasive adenocarcinoma that also contains a component of intraductal papillary mucinous neoplasm (IPMN) are eligible

    • The operating surgeon must document in the operative note that a complete gross excision of the primary tumor was achieved; the pathology report must include documentation of the margin status and the size of the tumor; the pathology report must also include the status of the three major margins—bile duct, pancreatic parenchyma, and retroperitoneal (uncinate)
  • Interval between definitive tumor-related surgery and 1st step registration between 21-70 days
  • Patients will be staged according to the 6th edition American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-3, N0-1, M-0 being eligible
  • Zubrod performance status 0 or 1
  • Complete history and physical examination including weight and Zubrod status within 31 days of study entry
  • Before starting therapy the patient should be able to maintain adequate oral nutrition of >= 1500 calories estimated caloric intake per day and be free of significant nausea and vomiting
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin (Hgb) >= 8.0 g/dL (transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable)
  • Post resection serum cancer antigen (CA)19-9 =< 180 units/mL within 21 days of registration on study
  • Serum total bilirubin =< twice the institutional upper limit of normal (ULN) within 21 days of registration on study
  • Creatinine levels =< twice the institutional upper limit of normal within 21 days of registration on study
  • Serum glutamic oxaloacetic transaminase (SGOT) must be =< 2.5 x institutional ULN within 21 days of registration on study
  • Negative serum pregnancy test for women of childbearing potential within 14 days of study registration
  • Abdominal/pelvic computed tomography (CT) scan with contrast is preferred; abdominal CT alone is acceptable only if insurance restrictions are experienced; chest CT/x-ray (CT of chest preferred) within 31 days of registration on study; patients allergic to intravenous (IV) contrast can have magnetic resonance imaging (MRI) of the abdomen/pelvis instead
  • Signed study-specific informed consent
  • Consultation, agreement, and documentation in the patient's chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol
  • Women of childbearing potential and male participants must practice adequate contraception
  • Patients with active human immunodeficiency virus (HIV) infection are eligible if their cluster of differentiation (CD)4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active antiretroviral treatment (HAART) is allowed

Exclusion Criteria:

  • Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN's that contain some secondary (minor) foci of adenocarcinoma are also not eligible
  • Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy
  • Prior systemic chemotherapy for pancreas cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Previous history of invasive malignancy (except non-melanoma skin cancer) unless the patient has been disease free for at least 2 years prior to study entry (patients with a previous history of carcinoma in situ are eligible)
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the 3 months of study registration
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Pregnant or lactating women
  • Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • If surgical margin status cannot be determined after consultation with the operating surgeon and the institutional pathologist, the patient will be ineligible
  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: NCT01013649

  Show 351 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Ross Abrams Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01013649     History of Changes
Other Study ID Numbers: NCI-2011-01987, NCI-2011-01987, RTOG-0848, CDR0000659092, RTOG 0848, RTOG-0848, U10CA021661, U10CA180868
Study First Received: November 13, 2009
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Adenocarcinoma
Carcinoma, Acinar Cell
Carcinoma
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorouracil
Gemcitabine
Capecitabine
Erlotinib
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 28, 2014