Primary objectives:To determine the objective tumor response (CR + PR) after 3 weeks of erlotinibSecondary objectives: To describe predictive markers for response:- radiological response (FDG-PET/CT)- EGFR mutations (HER1)To determine (diseasefree)…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Pathologic tumor response after 3 weeks of erlotinib
Secondary outcome
1. Radiological (CT) and metabolic (FDG-PET) response after 3 weeks of
treatment with erlotinib
2. Description of factors predictive for response:
- early metabolic response (FDG-PET after 3 days of treatment)
- molecular tumor characteristics, as EGFR mutations (HER1)
3. Toxicity of neoadjuvant treatment with erlotinib in combination with
surgical treatment
4.Overall survival, disease-free survival and locoregional control
Background summary
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (TK)
dysregulated in various tumor types. In NSCLC, the vast majority of tumors are
associated with aberrant or over-expressed EGFR. Erlotinib (Tarceva®) is a
reversible TK inhibitor with a favorable toxicity profile and can be orally
administered. Erlotinib as single agent showed objective response rates of
12-20% and overall survival benefit in patients with stage IIIB/IV NSCLC. Low
toxicity, significant and rapid tumor response rates suggest that erlotinib may
be used in the (neo)adjuvant setting.
The rationale for this study is to investigate whether erlotinib is able to
make an extra contribution to the curative treatment of early non-small cell
lung cancer (NSCLC). If erlotinib is able to induce responses in patients with
clinical stage I or II NSCLC, this agent might find a place in the
(neo)adjuvant setting.
This study will initially focus on a selected population to obtain proof of
principle whether induction treatment by erlotinib is able to induce tumor
responses in operable patients with clinical stage I or II NSCLC.
Patients with clinical stage I or II NSCLC who are more likely to respond to
erlotinib (i.e. non-smokers, patients with adenocarcinoma, females and patients
from Asiatic origin) will be entered first. The first evaluation will take
place after inclusion of 15 patients from this *enriched population*, serving
both for safety purposes and as a possibility to expand the study to patients
with other NSCLC subtypes.
Study objective
Primary objectives:
To determine the objective tumor response (CR + PR) after 3 weeks of erlotinib
Secondary objectives:
To describe predictive markers for response:
- radiological response (FDG-PET/CT)
- EGFR mutations (HER1)
To determine (diseasefree) survival and locoregional control
Study design
Phase II, open label, non-comparative, multicentre study
Intervention
erlotinib 150mg/day, oral dose, 1 hour before or 2 hours after a meal,
given once daily for 3 weeks, preoperative.
Study burden and risks
Burden associated with participation:
- Once a day one tablet of erlotinib for 3 weeks
- Two visits to the outpatient department
- Two FDG-PET scans
- One CT scan (thorax)
- One physical examination
- One blood withdrawal
Possible side-effects of treatment:
Common: rash, pruritus, dry skin and diarrhea.
Rare: Nausea, vomiting, stomatitis, abdominal pain, fatigue, dyspnea, cough,
anorexia, infection, conjunctivitis and keratoconjunctivitis sicca
Plesmanlaan 121
1066 CX Amsterdam
NL
Plesmanlaan 121
1066 CX Amsterdam
NL
Listed location countries
Age
Inclusion criteria
1. Patients who are candidates for lung resection for pathologically proven NSCLC or high (> 95%) probability of NSCLC based on medical history, chest X-ray, spiral CT-scan, bronchoscopy and [18F]-FDG-PET-scan
2. Clinical T1-3N1-0 stage (no mediastinal uptake on [18F]-FDG-PET imaging, negative endoscopic ultrasound guided fine needle aspiration cytology (EUS-FNA) or mediastinoscopy)
3. Primary lesion diameter considered measurable, the longest diameter being >=1 cm measured by spiral CT scan
4. For the first 15 eligible patients, two out of four of the following criteria apply:
a. Never smoker of ex-smoker (less than 10 pack years)
b. Female gender
c. Non-squamous histology
d. Asian origin
5. WHO performance status of 0/1
6. 18 years of age or older
7. Able to comply with study and follow-up procedures
8. For all females of childbearing potential a negative pregnancy test must be obtained within 72 hours before starting therapy
9. Patients with reproductive potential must use effective contraception
10. Informed consent to participate in the study
Exclusion criteria
1. Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure)
2. Current smoking
3. Prior therapy with systemic anti-tumor therapy with HER1/EGFR inhibitors (as small molecule or monoclonal antibody therapy)
4. Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions
5. The use of contact lenses
6. Patients who cannot take oral medication, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease
7. Nursing mothers
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-003927-35-NL |
| CCMO | NL13738.031.06 |