Clinical Trial: 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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: 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, by stopping them from dividing, or by stopping them from spreading. 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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine (gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as compared to gemcitabine alone following R0 or R1 resection of head of pancreas adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy following adjuvant gemcitabine based chemotherapy or non-gemcitabine based chemotherapy such as modified fluorouracil-leucovorin-irinotecan-oxaliplatin regimen (FOLFIRINOX) further enhances survival for such patients who are without evidence of progressive disease after 5 months of adjuvant chemotherapy. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after 5 months of adjuvant chemotherapy.

II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and without erlotinib for patients with resected head of pancreas adenocarcinoma.

III. To evaluate adverse events with and without erlotinib for patients with resected head of pancreas adenocarcinoma.

IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after adjuvant chemotherapy.

V. To evaluate preoperative cross-sectional im
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • 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 ]
    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 ]
    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.


Original Primary Outcome:

  • Overall survival of patients treated with gemcitabine hydrochloride with vs without erlotinib hydrochloride (first randomization)
  • Overall survival of patients treated with chemotherapy with vs without radiotherapy (second randomization)


Current Secondary Outcome:

  • Changes in fatigue as measured by the FACIT-F (primary) and the PROMIS derived short form (exploratory) [ Time Frame: Baseline up to 24 months ]
    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.
  • Disease-free survival [ Time Frame: Up to 11 years ]
    Disease-free survival will be estimated by the Kaplan-Meier method.
  • Frequency of objective criteria of resectability as measured by preoperative imaging [ Time Frame: Up to 11 years ]
  • 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 ]


Original Secondary Outcome:

  • Disease-free survival
  • Adverse events
  • Frequency of objective criteria of resectability as measured by preoperative imaging
  • Quality of life as measured by fatigue (FACIT-Fatigue and PROMIS-derived short form)
  • Laboratory correlative studies related to K-Ras in patients treated with gemcitabine hydrochloride with vs without erlotinib hydrochloride (first randomization)


Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 13, 2009
Date Started: November 2009
Date Completion:
Last Updated: May 17, 2017
Last Verified: May 2017