Investigate the activity and safety of amrubicin alone versus amrubicin incombination with cisplatin versus standard treatment for extensive disease(ED) small-cell lung cancer in the first line setting.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective tumor response, measured according to the RECIST criteria, will
be used as the principal endpoint in this trial. Disease assessments will be
preformed every 2 cycles.
Secondary outcome
Safety: This study will use the International Common Toxicity Criteria (CTCAE),
version 3.0, for toxicity and adverse event reporting.
progression-free survival (PFS)
overall survival (OS).
Background summary
The standard for treatment is Cisplatin with Etoposide. In Europe,
platinum-based combination chemotherapy has become the standard for the
treatment of extensive disease SCLC (ED SCLC). Results of treatment remain far
from satisfactory since virtually all patients die of disease and long term
survivors are very few (under 10%). One way to improve upon these results is
the incorporation of new agents into existing combinations.
The combination of amrubicin and cisplatin has demonstrated an impressive
response rate (87.8%) and MST (13.6 months) in Japanese patients with
previously untreated ED-SCLC while amrubicin single agent produced the response
rate of 76%. The majority of patients receiving the amrubicin regimen developed
neutropenia, but cardiotoxicity typical for anthracyclines was not common.
Therefore, a confirmation of these results in a non-Japanese
population is of interest. The single agent data, if confirmed, would make this
a preferable agent to a cisplatin combination in a significant number of
patients.
Study objective
Investigate the activity and safety of amrubicin alone versus amrubicin in
combination with cisplatin versus standard treatment for extensive disease
(ED) small-cell lung cancer in the first line setting.
Study design
This is an open randomized 3-arm multicenter late phase II study. Patients
will be stratified by WHO status, sex and institution. The primary endpoint
is response rate. A one-stage Fleming design has been used to design the
study.
Intervention
ARM 1: 3-weekly cycles of amrubicin (45 mg/m², days 1-3);
ARM 2: 3-weekly cycles of amrubicin (40 mg/m² days 1-3) + cisplatin (60
mg/m², day 1);
ARM 3: 3-weekly cycles of cisplatin (75mg/m², day 1) + etoposide
(intravenous injection 100 mg/m² on day 1, oral administration 200mg/m²
on days 2-3).
Treatment should start within 7 days of randomization.
Study burden and risks
At start of the study: anamnese (including medication intake), general
condition, medical history and physical examintaion. Before start of treatment
a CT of the head, thorax and abdomen are made. During treatment this will be
repeated every 6 weeks.
Before each chemotherapy treatment: blood sample, physical examination, adverse
events and concomitant medication.
An ECG and echocardiogram will be carried out before and at the end of
treatment. At the last visit:a physical examination, which may include an
assessment of sensory neurological clinical symptoms.
Avenue E. Mounierlaan 83/11
Brussel 1200 Bruxelles
België
Avenue E. Mounierlaan 83/11
Brussel 1200 Bruxelles
België
Listed location countries
Age
Inclusion criteria
-Histologically/cytologically proven small cell lung cancer
-WHO performance status 0-2
-Measurable disease according to RECIST criteria
-Age > 18 years
-Normal baseline cardiac function
-Adequate haematological function (WBC >1.5 x 10 9/L, platelets >100 x 10 9/L, Hb >9 g/dL)
-Creatinine clearance: > 60 ml/min (Cockcroft and Gault)
-Adequate hepatobiliary function (ALAT/AST <2.5 x Upper Limit of Normal)
-Written informed consent before randomization, according to ICH/EU GCP and national/local regulations
Exclusion criteria
-No prior systemic chemotherapy for small cell lung cancer
-No history of interstitial lung disease or pulmonary fibrosis
-No history of prior malignancy unless patient has been disease free for >5 years, or the tumour was a non-melanoma skin cancer or in-situ carcinoma of the cervix
-Absence of pre-existing peripheral neuropathy (CTCAE version 3.0 grade >1)
-Absence of uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV heart failure, uncontrolled angina, clinical significant pericardial disease or cardiac amyloidosis
-No pregnancy or breast feeding. Men and women of child bearing potential must use an appropriate method of contraception if the risk of conception exists
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 | EUCTR2006-001956-11-NL |
| CCMO | NL14506.018.06 |