ChemoRT With Adjuvant Chemo in Pancreatic Cancer (TARCEVA)

Study Overview
=================
Brief Summary
-----------------
To seek preliminary evidence of antitumor activity (progression free survival) of Erlotinib in combination with standard adjuvant chemoradiation and chemotherapy in patients with resected adenocarcinoma of the pancreas.

Detailed Description
-----------------
This study is a phase II trial of erlotinib in combination with chemoradiation in patients with stage I/II adenocarcinoma of the pancreas who are candidates for adjuvant chemoradiation. This study is a phase II trial of erlotinib in combination with chemoradiation in patients with resected stage I/II adenocarcinoma of the pancreas who are candidates for adjuvant chemoradiation. Eligible patients will receive adjuvant treatment with erlotinib 100 mg plus Capecitabine 800 mg/m2 PO BID (5 days on/ 2 days off regimen) and External Beam Radiation Therapy (EBRT) at doses of 50.4 Gy in 28 fractions after pancreatectomy (Dosing for capecitabine and erlotinib was amended after considering the toxicity profile of the first 6 patients). Approximately 4-8 weeks after the conclusion of chemoradiation, it is recommended patients will continue treatment with 4 cycles of gemcitabine 1000 mg/m2 days 1, 8, and 15 every 28 days plus daily erlotinib 100 mg. Eligible patients will receive adjuvant treatment with erlotinib 100 mg plus Capecitabine 800 mg/m2 PO BID (5 days on/ 2 days off) and External Beam Radiation Therapy (EBRT) to the tumor bed plus adjacent lymph nodes at doses of 50.4 Gy in 28 fractions after surgery. For patients with close or positive margins after resection, they will be able to receive 54.0 Gy over 30 fractions. Approximately 4-8 weeks after the conclusion of chemoradiation, it is recommended patients will continue treatment with 4 cycles of gemcitabine 1000 mg/m2 days 1, 8, and 15 every 28 days plus erlotinib 100 mg/daily.

Official Title
-----------------
Phase II Study of Erlotinib (TarcevaTM) Combined With Chemoradiation and Adjuvant Chemotherapy in Patients With Resectable Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: erlotinib hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Resection of a stage I/II pancreatic adenocarcinoma of the pancreas (R0/R1) and a candidate to receive postoperative adjuvant chemoradiation. R2 (laparoscopic resection) based on the surgeons operative note will be excluded from the study. Aged 18 years or older. ECOG performance status < 1. The effects of Erlotinib and Capecitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Patients must have normal organ and marrow function. Provision of written informed consent Patients must have a working knowledge of English in order to complete the quality of life questionnaires. Patients that do not meet this requirement will be exempt from the QoL assessment, but remain eligible for all other components of the study. Exclusion criteria Known severe hypersensitivity to Erlotinib any of the excipient of this product. Hypersensitivity to Capecitabine, doxifluridine, or 5-FU. Other coexisting malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma, non-invasive early stage bladder cancer (<T1), and cervical cancer in situ. Uncontrolled, intercurrent illness including (but not limited to) ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's Wort. Careful monitoring of PT/INR must be done for patients taking Warfarin. Incomplete healing from previous oncologic or other major surgery. Gastrointestinal tract disease resulting in an inability to take oral medication. Pregnant women are excluded from this study because Erlotinib is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Erlotinib, breastfeeding should be discontinued if the mother is treated with Erlotinib. Capecitabine is also potentially teratogenic and its metabolites can be found in breast milk. Patients with known AIDS or who are HIV-positive on anti-retroviral therapy are excluded since patients' immune deficiency are at increased risk of lethal infection when treated with marrow-suppressive therapy, and interactions between Erlotinib and anti-retroviral therapy are unknown. If patients have known risk factors of HIV they should be tested based on the discretion of the treating oncologist. Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded). Previous radiation to the abdomen. Previous chemotherapy for pancreatic cancer.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib and EBRT after pancreatectomy<br>Adjuvant treatment with erlotinib 100 mg plus Capecitabine 800 mg/m2 PO BID (5 days on/ 2 days off regimen) and External Beam Radiation Therapy (EBRT) at doses of 50.4 Gy in 28 fractions after pancreatectomy (Dosing for capecitabine and erlotinib was amended after considering the toxicity profile of the first 6 patients). Approximately 4-8 weeks after the conclusion of chemoradiation, it is recommended patients will continue treatment with 4 cycles of gemcitabine 1000 mg/m2 days 1, 8, and 15 every 28 days plus daily erlotinib 100 mg. | Drug: erlotinib hydrochloride<br>* Erlotinib 100 mg PO QD (1 hour prior to Capecitabine) (both given daily without interruption)<br>* Other names: Tarceva;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival | Time from surgery to recurrence | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events | Number of participants experiencing adverse events during chemoradiation and during adjuvant chemotherapy, Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. This is used to determine the Toxicity profile. | up to 3 years | 
| Change in Quality of Life (QoL) as Assessed by EORTC QLQ-C30 (Version 3.0) | Quality of life (QOL) was assessed before chemoradiation therapy (CRT) was started or during the first week of its administration [baseline (BL)], between completion of CRT and starting maintenance chemotherapy [time 1 (t1)], and within 3 months after completion of maintenance chemotherapy [time 2 (t2)]. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assesses quality of life on three domains: symptoms (score ranges from 7-14); function (score range 21-82); and global health status (score range 2-14). Higher or increasing scores mean worse outcomes; lower or decreasing scores mean better outcomes. | Up to 3 months after completion of maintenance chemotherapy | 
| Change in QoL as Assessed by QLQ-PAN 26 | Quality of life (QOL) was assessed before CRT was started or during the first week of its administration (baseline [BL]), between completion of CRT and starting maintenance chemotherapy (time 1 [t1]), and within 3 months after completion of maintenance chemotherapy (time 2 [t2]). QLQ-PAN 26 questionnaire includes 26 questions, organized into 7 scales, with scores for each ranging from 0-100. Higher scores indicate worse health state. Therefore, decreasing (negative) scores indicate a better outcome. | 3 months | 
| Time to Death as Assessed by Median Overall Survival (Months) |  | up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the pancreas, stage I pancreatic cancer, stage II pancreatic cancer