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Phase II Trial of Erlotinib in Advanced Pancreatic Cancer

Phase 2
18 Years
Open (Enrolling)
Cancer, Pancreas

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Trial Information

Phase II Trial of Erlotinib in Advanced Pancreatic Cancer

Erlotinib in addition to gemcitabine significantly improves overall survival compared to
gemcitabine alone in advanced pancreatic cancer (median overall survival 6.24 vs 5.91 months
respectively). However, combined therapy has not become standard of care due to the modest
absolute benefit. In NSCLC, the optimal efficacy of erlotinib is not in combination with
first-line cytotoxic chemotherapy for advanced disease, but as a single agent after cytoxic
chemotherapy. Preclinical and clinical data suggest that erlotinib will have activity as a
single agent in advanced pancreatic cancer. The presence of an erlotinib-induced rash is
associated with improved survival in phase II and III trials of diverse tumor types
(reviewed by Perez-Soler et al.), and is associated with higher steady state concentrations
of erlotinib.

This phase II trial aims to determine the safety and efficacy of erlotinib in patients with
advanced pancreatic cancer who have previously been treated with up to one prior line of
gemcitabine based chemotherapy for advanced disease. In addition, we will evaluate the
feasibility and activity of dose escalation of erlotinib in patients who do not develop a
rash. Clinical outcome will be correlated to EGFR status based on immunohistochemistry and
gene amplification status as well as Kras mutations from archival tumor tissue.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed pancreatic carcinoma
that is locally advanced, unresectable or metastatic.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan.

- Previous therapy:

Surgery: Previous surgery is permissible. Patients must be > 4 weeks from any major

- Chemotherapy: Patients may have received up to 1 prior line of gemcitabine based
systemic therapy (single agent or combination therapy) for locally advanced or
metastatic disease. Prior therapy with inhibitors of angiogenesis is permitted. All
toxicities must be resolved to < Grade 1 (CTCAE v 3.0) and the last dose must have
been given at least 4 weeks prior to randomization.

- Patients may also have received prior 5 FU (+/- folinic acid) or gemcitabine given
concurrently with radiation as a "radiation sensitizer". All toxicities must be
resolved and the last dose of chemotherapy must have been given at least 4 weeks
prior to randomization.

- Radiation: Patients may have received prior radiation treatment for management of
local disease providing that disease progression has been documented (either locally
or systemically), all toxicities have resolved, and the last fraction of radiation
treatment was completed at least 4 weeks prior to randomization.

- Age >18 years. Because no dosing or adverse event data are currently available on the
use of erlotinib in patients <18 years of age, children are excluded from this study
but will be eligible for future pediatric single-agent trials, if applicable.

- Life expectancy of greater than or equal to 3 months.

ECOG performance status <2.

- Patients must have normal organ and marrow function as defined below:

- Leukocytes >/= 3,000/mcL

- Absolute neutrophil count >/= 1,000/mcL

- Platelets >/= 100,000/mcL

- Total bilirubin
- Creatinine within normal institutional limits OR

- Creatinine clearance >/= 60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal

- Since CYP3A4 appears to be the major enzyme responsible for the human hepatic
metabolism of erlotinib in vitro, the concurrent use of inhibitors and inducers of
CYP3A4 are prohibited during the study treatment period. Concurrent use of CYP3A4
substrates are allowed, however, use caution and monitor the patient for potential
drug interactions.

- There is a potential interaction between erlotinib and warfarin. Patients have
experienced elevated INRs and bleeding with this combination of drugs. Patients on
warfarin with PT INR >1.5 are eligible provided that all of the following criteria
are met:

- The patient is therapeutic on a stable dose of warfarin

- The upper target for INR is no greater than 3.

- The patient has no active bleeding or pathological condition that carries a high risk
of bleeding (e.g., CT evidence of tumor invading the duodenum or known varices).

Note: anticoagulation with low molecular weight heparin is permitted.

- The effects of erlotinib 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;
abstinence) 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.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients receiving any other investigational agents concurrently are ineligible.

- Prior therapy with inhibitors of the EGFR (eg. cetuximab, EMD 72000, panitumumab,
gefitinib, erlotinib) or multitargeted agents that inhibit EGFR (eg. ZD6474, AEE788).

- Patients with allergies to or a history of allergic reactions attributed to any other
compound of similar chemical or biologic composition to erlotinib.

- Patients with greater than grade 1 diarrhea at baseline. Patients with pancreatic
cancer often have diarrhea due to pancreatic insufficiency, so a trial of pancreatic
enzymes may be warranted to reduce baseline diarrhea.

- PT INR >1.5 unless the patient is on full-dose warfarin.

- Patients with any condition that impairs their ability to swallow and retain pills

- Patients with known brain metastases will be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse

- Uncontrolled intercurrent illness including, but not limited to, uncontrolled
hypertension, 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.

- Pregnant women are excluded from this study because erlotinib has the potential for
teratogenic or abortifacient effects. 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

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with erlotinib. Appropriate studies
will be undertaken in patients receiving combination antiretroviral therapy when

Type of Study:


Study Design:

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

Outcome Measure:

Primary objective: To determine the efficacy of erlotinib, as measured by the rate of disease control (objective response plus prolonged stable disease), in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma.

Outcome Time Frame:

Clinically assessed every cycle (month) and radiologically assessed every 2 cycles (2 months) with CT scan

Safety Issue:


Principal Investigator

Malcolm Moore, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Drug Development Program, Princess Margaret Hospital


Canada: Ethics Review Committee

Study ID:




Start Date:

November 2006

Completion Date:

Related Keywords:

  • Cancer
  • Pancreas
  • Pancreatic Cancer
  • Pancreatic Carcinoma
  • Pancreas
  • Adenocarcinoma
  • Erlotinib
  • Tarceva
  • OSI-774
  • Phase II
  • Pancreatic Neoplasms