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UAB 0808, A Phase II Study of Short-course Preoperative Erlotinib Followed by Post-operative Erlotinib-gemcitabine in Patients With Resectable Pancreatic Adenocarcinoma

Phase 2
19 Years
80 Years
Not Enrolling
Pancreatic Cancer

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Trial Information

UAB 0808, A Phase II Study of Short-course Preoperative Erlotinib Followed by Post-operative Erlotinib-gemcitabine in Patients With Resectable Pancreatic Adenocarcinoma

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 ERK; expression of c-fos), and 2) prediction of
sensitivity based on a "static" analyte (detection of 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.

Inclusion Criteria:

.Histologic or cytologic confirmation of pancreatic ductal adenocarcinoma.

- Pancreatic cancer must be surgically resectable: a) no evidence of distant
metastasis; b) clear fat plane around the celiac and superior mesenteric arteries; c)
patent portal and superior mesenteric veins

- No evidence of post-resection distant metastasis

- Pathologic confirmation of R0/R1 status following surgical resection

- Age ≥ 19 years

- Male or female gender (not pregnant or lactating). If the subject is fertile, use
of medically acceptable contraception will be required.

- Patient should be able to understand and offer signed written informed consent prior
to study entry.

- No prior receipt of chemotherapy or radiotherapy

- Patients must demonstrate a ECOG P.S. of 0 or 1

- End Organ function must be adequate meeting the below criteria at baseline:

WBC> 3000/mm3, ANC> 1500/mm3, PLT>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) PT/PTT below the
upper limit of normal

Exclusion Criteria:

- Diagnosis of active (treated in past 5 years) concomitant malignancy with exception
of non-melanotic skin cancer

- Transplant patients or patients receiving immunosuppression

- Presence of an underlying disease state associated with active bleeding or a past
medical history of coagulopathy

- New York Heart Association Class IV congestive heart failure

- Limited mental capacity or language skills to the extent simple instructions cannot
be followed or information regarding adverse events cannot be provided

- History of non-compliance with prescribed medical care

Post-Operative Phase Inclusion

- No Evidence of Post-Resection Distant Metastasis

- Pathological confirmation of R0/R1 status following Surgical resection

- Patient must demonstrate a post-operative performance status of 0 or 1.

- End Organ function must be adequate, meeting the below criteria at baseline:

1. WBC > 3000/mm³,ANC > 1500/mm³, Platelets > 100,000 mm³

2. Calculated Creatinine Clearance > 50 ml/min,Serum Creatinine < 1.5 mg/dl

3. Bilirubin < 3.0 mg/dl; AST and ALT < 3 x normal value

4. PT/PTT/INR within normal Limits.


Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

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

Outcome Time Frame:

End of the study

Safety Issue:


Principal Investigator

Juan P Arnoletti, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham


United States: Institutional Review Board

Study ID:




Start Date:

February 2009

Completion Date:

July 2011

Related Keywords:

  • Pancreatic Cancer
  • Pancreatic
  • Cancer
  • Assay
  • Biomarkers
  • Pancreatic Neoplasms



University of Alabama at Birmingham,Comprehensive Cancer Center Birmingham, Alabama  35294-0016