Clinical trial NCT00313560: ChemoRT With Adjuvant Chemo in Pancreatic Cancer (TARCEVA)
Official title: Phase II Study of Erlotinib (TarcevaTM) Combined With Chemoradiation and Adjuvant Chemotherapy in Patients With Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria

1. 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.
2. Aged 18 years or older.
3. ECOG performance status \< 1.
4. 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.
5. Patients must have normal organ and marrow function.
6. Provision of written informed consent
7. 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

1. Known severe hypersensitivity to Erlotinib any of the excipient of this product. Hypersensitivity to Capecitabine, doxifluridine, or 5-FU.
2. 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.
3. 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.
4. 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.
5. Incomplete healing from previous oncologic or other major surgery.
6. Gastrointestinal tract disease resulting in an inability to take oral medication.
7. 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.
8. 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.
9. Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).
10. Previous radiation to the abdomen.
11. Previous chemotherapy for pancreatic cancer.

Primary outcomes:
measure: Recurrence Free Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: up to 3 years
measure: Change in Quality of Life (QoL) as Assessed by EORTC QLQ-C30 (Version 3.0)
timeFrame: Up to 3 months after completion of maintenance chemotherapy
measure: Change in QoL as Assessed by QLQ-PAN 26
timeFrame: 3 months
measure: Time to Death as Assessed by Median Overall Survival (Months)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Amol Narang, MD
role: STUDY_CHAIR
References:
citation: Herman JM, Fan KY, Wild AT, Hacker-Prietz A, Wood LD, Blackford AL, Ellsworth S, Zheng L, Le DT, De Jesus-Acosta A, Hidalgo M, Donehower RC, Schulick RD, Edil BH, Choti MA, Hruban RH, Pawlik TM, Cameron JL, Laheru DA, Wolfgang CL. Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):678-85. doi: 10.1016/j.ijrobp.2013.03.032.