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Phase II Trial of Epidermal Growth Factor Ointment for Patients With Erlotinib Related Skin Effects

Phase 2
20 Years
Open (Enrolling)
Non-small Cell Lung Cancer, Pancreatic Cancer

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Trial Information

Phase II Trial of Epidermal Growth Factor Ointment for Patients With Erlotinib Related Skin Effects


Advances in the knowledge of tumor biology and mechanisms of oncogenesis has granted the
singling out of several molecular targets for NSCLC treatment. Among these targets,
epidermal growth factor receptor (EGFR), or HER1, has received particular attention in lung
cancer treatment. EGFR is a transmembrane receptor found primarily on cells of epithelial
origin. Autophosphorylation of its intracellular domain initiates a cascade of events
leading to cell proliferation. EGFR is commonly expressed at a high level in a variety of
solid tumors and it has been implicated in the control of cell survival, proliferation,
metastasis and angiogenesis. The main pharmacological strategies in clinical development for
therapeutic inhibition of EGFR are monoclonal antibodies to antagonize ligand-receptor
binding, and small-molecules to inhibit tyrosine kinase domain activation. The main EGFR
inhibitors are cetuximab, an anti-EGFR monoclonal antibody, and Erlotinib an EGFRtyrosine
kinase inhibitor. The key indications for clinical use are colorectal cancer and head and
neck cancer for cetuximab and NSCLC for Erlotinib. Erlotinib, a quinazolin-4-amine, is a
highly potent, orally available, reversible inhibitor of EGFR tyrosine kinase. Erlotinib, in
a phase III randomized placebo-controlled trial, has been proven to prolong survival (6.7
months versus 4.7 months for Erlotinib and for placebo respectively, p = 0.001) in NSCLC
patients after first or second line chemotherapy. The analysis of quality of life and time
to deterioration of patients reported symptoms showed statistically and clinically
meaningful benefit for patients randomized to Erlotinib. Moreover, Erlotinib resulted active
(response rate of 8.9%) and safe (only 5% of patients discontinued treatment for toxicity).
Following this trial, Erlotinib has been approved by Food and Drug Administration and
Committee for Medicinal Products for Human use in chemotherapy-pretreated advanced NSCLC.
Skin rash is a common side-effect of all HER1/EGFR inhibitors.

EGF ointment

Rash affecting the skin above the waist, is the most common adverse event associated with
Erlotinib, and generally develops within 7-10 days of starting treatment. Skin rash may
spontaneously resolve and reappear and it is reversible following drug discontinuation.
However, when it develops, this chronic side-effect is very distressing for the patient. The
increasing use of EGFR-targeted agents and specifically of Erlotinib in NSCLC treatment, and
simultaneously the lack of clinical trials on this topic, makes rash management and etiology
investigation high priorities.

It has been reported that repeated treatment with EGF increases the epithelial cell
proliferation in a dose dependent manner and accelerates the wound healing process, whereas
a single EGF treatment has no noticeable effect on the wound-healing rate. There have been
many studies aimed at developing a topical formulation with the sustained and stable
pharmacological properties of recombinant human EGF (rhEGF). And the rh-EGF concentration
between 1 and 5 ug/g can be seen as the ideal concentration to achieve the most efficient
results for acute wounds with partial thickness defects.

Inclusion Criteria:

- Age :older than 20

- ECOG performance status 0 -2

- Histologically lung cancer or Pancreatic Cancer

- Patients take Erlotinib following the reason Clinical failure of the prior therapy
locally advanced or metastatic NSCLC The 1ST line using in combination with
Gemcitabine for locally advanced, unresectable or metastatic Pancreatic

- Patients who have Erlotinib-treatment related skin lesions Gr≥2 (NCI-CTC V3.0).

- A patient with at least one measurable primary lesion of which the diameter is
confirmed to be 10mm in Spiral CT or multidetector CT (MD CT), or 20 mm or longer in
conventional CT (it should be used by a consistent method during the study period).

- The following laboratory test results:

Creatinine clearance ≥ 60ml/min Number of absolute neutrophil counts (ANC) > 1.5 x 109/L
Number of thrombocytes > 100 x 109/L Total bilirubin < 2x upper limit of normal ALAT, ASAT
< 3 x upper limit of normal (in case of liver metastasis, 5 x upper limit of normal)
Alkaline phosphatase < 3 x upper limit of normal (in case of liver metastasis, 5 x upper
limit of normal)

- A patient with the willingness to comply with the study protocol during the study
period and capable of complying with it.

- A patient who signed the informed consent prior to the participation of the study and
who understands that he/she has a right to withdrawal from participation in the study
at any time without any disadvantages.

Exclusion Criteria:

- A patient with previous active or passive immunotherapy.

- A pregnant or lactating patient

- A patient of childbearing potential without being tested for pregnancy at baseline
for positive. (A postmenopausal woman with the amenorrhea period of at least 12
months or longer is considered to have non-childbearing potential.)

- A patient with history of uncontrolled seizures, central nervous system disorder or
psychiatric disorders that are considered clinically significant by the investigator
that would prohibit the understanding of informed consent or that may be considered
to interfere with the compliance of the administration of the study medications.

- A patient with history of dermatologic care (except transient urticaria) within 4

- A patient with clinically significant (i.e. active) heart disease (e.g. congestive
heart failure, symptomatic coronary artery diseases, cardiac arrhythmias, etc) or
myocardial infarction within past 12 months.

- A patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.

- Organ allogenic transplantation requiring immunosuppressive therapy. Any waiver of
these inclusion and exclusion criteria must be approved by the investigator and the
sponsor on a case-by case basis prior to enrolling the subject.

- Known allergies, hypersensitivity, or intolerance to Study drugs, Chemotherapy drugs
using this Clinical trial

Type of Study:


Study Design:

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

Outcome Measure:

Improvement of skin lesion grading by NCI-CTC v3.0

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Sung Yong Oh, M.D.,Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Onclogy Division, Dong-A University Hospital


Korea: Food and Drug Administration

Study ID:




Start Date:

May 2012

Completion Date:

November 2014

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Pancreatic Cancer
  • Erlotinib
  • Skin side effect
  • EGF ointment
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Pancreatic Neoplasms