Primary objectives:1. Determine the potential improvement of the duration of progression-free survival by maintenance treatment with gemcitabine. Secondary objectives:1. To compare the objective radiological response (ORR) rate2. To compare overall…
ID
Source
Brief title
Condition
- Mesotheliomas
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is progression free survival, defined as time from
randomisation to disease progression or death (in case no progression has been
documented)
Secondary outcome
- Adverse events
- Objective radiological response rate in patients with measurable disease
- Overall survival
- Changes in vital capacity and FEV1.
Exploratory endpoints include:
- biomarker analysis
- germline polymorphisms of relevant candidate genes
- new techniques to analyse standard imaging data
Background summary
Malignant mesothelioma (MM) is a nearly invariably lethal tumor of the pleura
or peritoneum. Evidence from both mesothelioma studies and other solid
malignancies indicates the potential to deliver real benefits to patients using
a maintenance chemotherapy strategy.
The aim of this study is to perform a randomised phase II clinical trial to
characterise the potential clinical benefit, toxicity, and biomarkers of
outcome for maintenance chemotherapy with gemcitabine in patients with
malignant pleural mesothelioma who have completed first line chemotherapy
without progression. The choice of gemcitabine builds on previous work in
mesothelioma and non-small cell lung cancer, which proposes a non-cross
resistant *switch maintenance* agent.
Study objective
Primary objectives:
1. Determine the potential improvement of the duration of progression-free
survival by maintenance treatment with gemcitabine.
Secondary objectives:
1. To compare the objective radiological response (ORR) rate
2. To compare overall survival (OS)
3. To assess and compare the lung function
4. To describe the toxicity
5. To identify potential biomarkers
Exploratory objectives:
1. To correlate tumour biomarkers and SNP*s with PFS and severe toxicity
2. To explore new techniques to analyse standard imaging data
Study design
This is a randomised, phase II multicentre trial of maintenance single agent
gemcitabine or best supportive care in patients with malignant pleural
mesothelioma who have completed first line chemotherapy without progression.
Intervention
Treatment with Gemcitabine or best supportive care.
Gemcitabine will be given intravenously at day 1 and day 8 of a 3-weeks cycle
at a dose of 1250 mg/m2. Study treatment will continue until disease
progression; unacceptable grade 3 or 4 treatment toxicity; serious intercurrent
illness; patient request for discontinuation; need or use for any other
anti-cancer agent other than protocol treatment, except for palliative
radiotherapy.
Study burden and risks
Risks: side effects of Gemcitabine
Burden: the extent of the burden for the patient is less. A lot of tests which
the patient should have undergone are common practise, but more frequently
done.
Additional investigations will be done for start of the study at all
participants: extra bloodsampling for genotyping, biomarker and immunological
research, lung function examination. On day 22, before second course and every
6 weeks on the same day as the response evaluation extra bloodsampling will be
taken for immunological research at the participants in the pilot study. The
extra blood tests will take place combined with the routine laboratory tests,
so the patient doesn't have to be pricked extra. The CT scan is done by
default. The standard CT-scan and a lung function examination will be done
every 6 weeks on everyone and every 3 weeks a routine laboratory testing will
be done. Only on patients who have randomized for the Gemcitabine arm, blood
(haematology) will be taken off on day 8 to determine whether the patient is
able to get the chemotherapy treatment.
Luijbenstraat 15
's Hertogenbosch 5211 BR
NL
Luijbenstraat 15
's Hertogenbosch 5211 BR
NL
Listed location countries
Age
Inclusion criteria
• Patients with histologically or cytologically proven malignant mesothelioma •
Age >= 18 years. • At the date of randomisation, the patients must have
completed 4 cycles of first-line chemotherapy with a platinum (cisplatin or
carboplatin) and pemetrexed combination at least 21 days but no more than 42
days prior to study entry, and have no evidence of progressive disease
following first-line treatment. • Measurable or evaluable disease, according to
modified RECIST criteria for pleural mesothelioma. • Ability to understand the
study and give signed informed consent prior to beginning of protocol specific
procedures. • WHO performance status <= 2 • Adequate organ function as evidenced
by the following peripheral blood counts or serum chemistries at study entry: -
Hematology: Neutrophil count >= 1.5 x 109/l, Platelets >= 100 x 109/l, Hemoglobin
>= 6.2 mmol/l. - Hepatic function as defined by serum bilirubin <= 1.25 times the
upper limit of normal (ULN), ALT and AST <= 2.5 times the ULN, except if liver
metastases then ALAT and ASAT < 5 times the ULN. - Renal function as defined by
serum creatinine <= 1.25 times ULN or creatinine clearance >= 50 ml/min (by
Cockcroft-Gault formula).
Exclusion criteria
• Active uncontrolled infection or severe cardiac dysfunction (such as New York
Heart Association Class III or IV cardiac disease, myocardial infarction within
the last 6 months, unstable arrhythmias, or unstable angina).
• Presence of symptomatic CNS metastases.
• Radiotherapy within 2 weeks prior to study entry.
• Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling
condition.
• Concomitant administration of any other experimental drugs under
investigation.
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005834-12-NL |
| CCMO | NL43041.031.13 |