To estimate the efficacy of erlotinib administered as a single agent to chemo-naïve NSCLC patients as determined by the non progression rate (NPR) at 8 weeks.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the non progression rate (NPR). The NPR is
defined as the proportion of patients without progression (based on RECIST
criteria) at 8 weeks after start of treatment, i.e. all patients with a
response rating of Complete Response (CR), Partial Response (PR), or Stable
Disease (SD) according to RECIST that is documented for at least 8 weeks from
baseline.
Secondary outcome
Secondary efficacy parameters include overall response rate using RECIST
criteria, response duration, time to progression, progression-free survival and
overall survival.
Background summary
Never smokers with NSCLC appear to derive better clinical benefit (eg, higher
response rateds, longer survival) from epidermal growth factor receptor (EGFR)
inhibitors than former/current smokers. Current smokers were found to have as
much as a 2-fold decrease in erlotinib trough plasma concentrations than former
or never smoking patients, PK could contribute to the differences in efficacy
and suggest higher doses may be required in current smokers. In the phase II
setting, significant antitumour activity was demonstrated with first-line
erlotinib monotherapy. Erlotinib administered as single agent as first line
treatment option in advanced NSCLC was well tolerated with mainley
mild-to-moderate treatment-related AEs (rash and diarrhoea). Based on these
results, erlotinib has potential as first-line treatment option in advanced
NSCLC and further study in this setting is recommended.
Study objective
To estimate the efficacy of erlotinib administered as a single agent to
chemo-naïve NSCLC patients as determined by the non progression rate (NPR) at 8
weeks.
Study design
This is an parallel, open-label, phase II, non-randomized study. Groups are
defined by smoking status. This study will be performed at 11 centres within
Europe. Approximately 44 patients will be enrolled in total. Histological
tumour samples are mandatory and will be collected at screening. After
successful completion of all screening procedures, patients will start on
therapy with daily dosing. For the group of current/former smoker patients the
starting dose will be 150 mg/day escalating up to a maximum of 300 mg/day
according to the safety profile in order to determine the optimum dose in this
population.Treatment will continue until PD, unacceptable toxicity or death.
Subsequently, for a subset of 10 patients in both groups, a full PK assessment
will be done. Minimal PK sampling will be done in all the other patients. PK
sampling during study should be done at day 14 and day 42. Selected study
centres will participate in the full PK sampling procedures. For all patients*
safety and efficacy assesments will be scheduled as per the schedule of
assesments (page 34, table 3 of the protocol)
Intervention
For the group of non-smoker patients, the daily dose will be 150 mg/day.
For the group of current/former smoker patients the starting dose will be 150
mg/day escalating up to a maximum of 300 mg/day according to the safety profile
in order to determine the optimum dose in this population.Treatment will
continue until PD, unacceptable toxicity or death.
Study burden and risks
Every patient will be treated for approximately 12 months followed by
follow-up. During the treatment phase patients who entered the full PK group,
will have up to 16 visits, these visits will involve about 25 hours in total.
30 bloodsamples will be taken (a cannule is optional) and 4 MRI/CT*s and one
bronchoscopy assesments performed. The minimal PK group has approximately 10
visits, involving 12 hours and 20 bloodsamples(a cannule is optional) and 4
MRI/CT*s and one bronchoscopy assesments are performed. Major (rare)
complications after a biopsy by bronchoscopy are low blood oxygen,
pneumothrorax and arrhytmia. The most frequent side effects seen so far with
erlotinib are in approximately 75% of patients rash, it generally improves
without treatment (self-limiting). Other side effects are diarrhoea, fatigue,
nausea ,vomiting and a dry skin. There may also be a risk of irreversible
corneal lesions; this risk is increased in patients wearing contact lenses.
Laboratory abnormalities were observed infrequently with erlotinib when used
alone. Based on animal studies, there may also be a risk of side effects that
involve your liver, kidneys, eyes, ovaries, or hair follicles. Because of the
way erlotinib is metabolized (broken down by the body), there is a possibility
of an interaction between erlotinib and a certain type of anti-coagulant (blood
thinner). The long-term effects of erlotinib are unknown.
Grenzacherstreet 183
CH-4070 Bazel
Switherland
Grenzacherstreet 183
CH-4070 Bazel
Switherland
Listed location countries
Age
Inclusion criteria
- Patients with histological documented, locally advanced or recurrent (stage IIIB and not amenable for combined modality treatment) or metastatic (Stage IV) NSCLC who have not received prior chemotherapy for advanced disease.
- Formalin-fixed, paraffin-embedded primary diagnosis lung tumour tissue samples (tissue blocks are preferred over slides) representative of the tumour and collected prior to starting erlotinib therapy will be provided to the co-ordinating investigator within 3 weeks of the patient starting erlotinib therapy. This Is A Mandatory Requirement For Study Entry
- No prior chemotherapy for advanced disease. Previous adjuvant treatment is permitted if patient relapsed * 1 year after the end of the chemotherapy.
- Measurable disease according to RECIST.
- Age 18 or greater.
- Able to comply with study and follow-up procedures.
- Patients must be able to take oral medication.
- Written (signed) Informed Consent (WIC) to participate in the study.
- ECOG performance status of 0 - 2.
- Life expectancy of at least 12 weeks.
- At least 4 weeks since any prior surgery or radiotherapy. Patients must have recovered (CTC < 1) from acute toxicities of any previous therapy.
- Granulocyte count > 1,500/mm3 and platelet count > 100,000/mm3; Haemoglobin * 9.0g/dl.
- Serum bilirubin within upper limit of normal (ULN), SGOT (AST) and SGPT (ALT) < 2.5 x ULN (or * 5 x ULN in case of liver metastases).
- Serum creatinine * 1.5 ULN or creatinine clearance * 60 ml/min.
- For all females of childbearing potential a negative pregnancy test must be obtained within 72 hours before starting therapy. Patients with reproductive potential must use effective contraception.
- Patients that either can be classified as never smokers or as current/former smokers according to the definitions in section 3.1 (note that all other smokers (e.g. cigar, pipe) will be excluded from study participation).
Exclusion criteria
1. Any unstable systemic disease including:
- active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol treatment,
- uncontrolled hypertension,
- unstable angina,
- severe heart disease (NYHA stages III and IV heart failure, unstable angina, uncontrolled arrhythmia in particular)
congestive heart failure,
- history of myocardial infarction within the previous year,
- serious cardiac arrhythmia requiring medication,
- hepatic, renal or metabolic disease,
2. Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
3. Patients are excluded if they have clinical evidence of brain metastasis, or have brain metastasis or spinal cord compression that is newly diagnosed and/or has not yet been definitively treated with surgery and/or radiation; previously diagnosed and treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for at least 2 months will also cause patients to be excluded.
4. Any diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the study medication.
5. Previous treatment with any therapy which acts on the EGFR axis.
6. Patients unable to take oral medication, requiring intravenous alimentation, who have mal-absorption syndrome or any other condition affecting gastrointestinal absorption, or who have active peptic ulcer disease.
7. Nursing and/or pregnant women.
8. Any inflammatory changes of the surface of the eye.
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 | EUCTR2005-004782-41-NL |
| CCMO | NL11276.029.06 |