7 Day's of Erlotinib Neo-adjuvant, Followed by Adjuvant Erlotinib-gemcitabine in Pancreatic Cancer Patients
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|ClinicalTrials.gov Identifier: NCT00841035|
Recruitment Status : Terminated (Sponsor stopped due to slow enrollment)
First Posted : February 11, 2009
Results First Posted : October 6, 2014
Last Update Posted : May 19, 2017
|First Submitted Date ICMJE||February 9, 2009|
|First Posted Date ICMJE||February 11, 2009|
|Results First Submitted Date ICMJE||July 3, 2013|
|Results First Posted Date ICMJE||October 6, 2014|
|Last Update Posted Date||May 19, 2017|
|Study Start Date ICMJE||February 2009|
|Actual Primary Completion Date||July 2011 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Epidermal Growth Factor Receptor Signaling(EGFR) in the Presence of Pancreatic Tumor Related to the Mechanism to Erlotinib. [ Time Frame: During the trial only ]
It was our belief that we would need a comprehensive analysis of a dynamic panel of biomarkers relevant to EGFR signaling as well as the erlotinib mechanism of action it seems more useful in that sense. Furthermore,the ability limited of pancreatic cancer tissue sampling precluded biomarker correlation assays.These could not be worked out in either a xenograft model or in in-vitro conditions.
|Original Primary Outcome Measures ICMJE
||The primary objective is to determine the effects of short course preoperative erlotinib in a panel of predictive pancreatic cancer biomarkers among patients treated with surgical resection [ Time Frame: End of the study ]|
|Change History||Complete list of historical versions of study NCT00841035 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||The Secondary Objectives Include Analysis of Recurrence-free and Overall Survival and the Development of a Predictive Assay for Response to Erlotinib Based on Selected Bio-markers in Endoscopic Ultrasound-Fine-needle Aspiration Specimens. [ Time Frame: End of the study ]
The measurement was to be the average length of time before recurrence of disease and the overall survival time. As well as time from recurrence to death in subjects.This time will be measure in months till recurrence and them months to death.
|Original Secondary Outcome Measures ICMJE
||The secondary objectives include analysis of recurrence-free and overall survival and the development of a predictive assay for response to erlotinib based on selected biomarkers in EUS-FNA specimens obtained at the time of pancreatic cancer diagnosis. [ Time Frame: End of the study ]|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||7 Day's of Erlotinib Neo-adjuvant, Followed by Adjuvant Erlotinib-gemcitabine in Pancreatic Cancer Patients|
|Official Title ICMJE||University of Alabama at Birmingham(UAB 0808), A Phase II Study of Short-course Preoperative Erlotinib Followed by Post-operative Erlotinib-gemcitabine in Patients With Resectable Pancreatic Adenocarcinoma|
1.1 Primary Objective
To evaluate the effects of short course preoperative erlotinib treatment in a panel of predictive biomarkers from a group of patients who undergo resection of pancreatic adenocarcinoma with curative intent.
1.2 Secondary Objectives
1.2.1 To analyze the effects of short course preoperative erlotinib treatment followed by postoperative erlotinib-gemcitabine therapy in the disease-free survival of patients who undergo curative intent resection of pancreatic adenocarcinoma.
1.2.2 To evaluate secondary endpoints of disease response such as duration of overall survival and patterns of recurrence for patients with resectable pancreatic cancer who undergo this treatment regimen.
1.2.3 To evaluate the plasma pharmacokinetics of erlotinib in pancreatic cancer patients both in the preoperative and postoperative setting, and to explore correlations between plasma and tumor erlotinib concentrations.
1.2.4 To develop a clinically relevant predictive assay of response to erlotinib based on selected biomarkers in endoscopic ultrasound-fine needle aspiration (EUS-FNA) specimens when it can be obtained at the time of pancreatic cancer diagnosis in chemotherapy-naive patients.
Our current clinical trial proposal includes a short course of pre-operative, single agent erlotinib followed by post-operative erlotinib-gemcitabine in a neo-adjuvant/adjuvant approach to the treatment of patients with resectable pancreatic adenocarcinoma. The short course pre-operative erlotinib treatment serves two objectives: 1) erlotinib, through its cytostatic effects, may hinder the ability of tumor cells to metastasize at the time of surgical resection with minimal toxic effects and no delay in surgical treatment; 2) the true effects of erlotinib on potential determinants of response can be best assayed on the pancreatic cancer itself since no other model can better resemble the patients authentic tumor microenvironment. The post-operative treatment component of the protocol attempts to improve the demonstrated effects of gemcitabine by adding erlotinib in the adjuvant setting, a drug combination that, as mentioned, has already been proven to be advantageous for patients with advanced pancreatic cancer.
Traditionally, chemotherapy for cancer has been conducted in an empiric fashion by first selecting a regimen based on clinical trial evidence and clinical parameters, and then by assessing the objective response to that regimen employing clinical and radiographic imaging means. This approach suffers from many disadvantages, most conspicuously the inability to select the better patient candidates prior to the initiation of therapy, thus sparing the risk and expense of ineffective treatment for patients who are unlikely to respond. Since pancreatic cancer expression of EGFR protein by itself is not predictive of therapeutic response, alternative methods of patient selection seem to be essential for the success of EGFR-targeted treatment. The understanding of EGFR molecular signaling has allowed the drug development process to shift from an empiric random screening approach to a more rational and mechanistic, target-directed approach. Among multiple attempts to identify molecular determinants of tumor cell sensitivity to EGFR inhibitors, there are two main paradigms that stand out: 1) activation of downstream pharmacodynamic effectors associated with response to the drug (i.e. phosphorylation of Akt or extracellular signal-regulated kinase (ERK); expression of c-fos), and 2) prediction of sensitivity based on a "static" analyte (detection of epidermal growth factor receptor (EGFR) sensitizing mutations; epithelial-mesenchymal transition profile). However, given the complexity of factors governing pancreatic cancer response to erlotinib, the biologic heterogeneity of malignant phenotype, and overall relatively low response rates, we believe that it is unlikely that analysis of a single biomarker will be useful for patient selection. A comprehensive analysis of a dynamic panel of biomarkers relevant to EGFR signaling and erlotinib mechanism of action seems more useful in that sense. Furthermore, the limited ability of pancreatic cancer tissue sampling often precludes biomarker correlation to assays worked out in xenograft models or in-vitro conditions.
The translational rationale of this proposal is therefore to develop predictive chemotherapy sensitivity-resistance assays (CSRA) for pancreas carcinoma patients treated with erlotinib and gemcitabine. This will represent a major advance, because the CSRA would enable prediction of clinical response prior to initiation of therapy.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Pancreatic Cancer|
|Intervention ICMJE||Drug: erlotinib
Preoperative dosing of 150 mg oral erlotinib for 7 days before surgery. followed by erlotinib 100 mg daily 6 month/6 chemotherapy cycles. Gemcitabine 1000 m2 weekly after surgery for 6 cycles.
Other Name: Tarceva
|Study Arms ICMJE||Experimental: Eroltinib added to standard of care
150 mg of erlotinib for 7 days prior to surgery,then in the adjuvant stage the subject will receive 100mg of erlotinib and gemcitabine 1000mg/2 for 6 cycles
Intervention: Drug: erlotinib
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||July 2011|
|Actual Primary Completion Date||July 2011 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
.Histologic or cytologic confirmation of pancreatic ductal adenocarcinoma.
White Blood Cell Count (WBC)> 3000/mm3, absolute neutrophil count(ANC)> 1500/mm3, Platelets>100,000mm3 Calculated creatinine clearance >50 ml/min, normal serum creatinine (mg/dL) (if calculated Crcl <50 ml/min, Crcl should measured and be > 50 ml/min) Bilirubin <3.0 mg/dL (patients with obstructive jaundice require preoperative endoscopic biliary stenting if total bilirubin >3.0 mg/dl) prothrombin time(PT) /partial thromboplastin time(PTT) below the upper limit of normal
Post-Operative Phase Inclusion
|Ages ICMJE||19 Years to 80 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00841035|
|Other Study ID Numbers ICMJE||F080718006|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Marty Heslin, University of Alabama at Birmingham|
|Study Sponsor ICMJE||University of Alabama at Birmingham|
|Collaborators ICMJE||OSI Pharmaceuticals|
|PRS Account||University of Alabama at Birmingham|
|Verification Date||April 2017|
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