The aim of this study is to evaluate the efficacy of a personalized drug profiling method using short-term cultures of malignant cells derived from the patient*s pleural fluid.
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 endpoint is accuracy of the drug profiling method, defined by the
number of truly predicted responses, as a percentage of the total number of
patients in the study.
Secondary outcome
Secondary endpoints include objective response rate (ORR), progression free
survival (PFS), overall survival (OS), pulmonary function and frequency and
severity of adverse events. Exploratory endpoints to identify potential
biomarkers include genomic profiling, assessment of breath prints of Volatile
Organic Compounds by E-nose.
Background summary
Prognosis of malignant pleural mesothelioma is extremely poor. There is no
standard second line therapy for these patients. For metastatic NSCLC, the
registrated third line therapy (erlotinib), is ineffective in the majority of
these patients. We hypothesize that a personalized drug profiling method will
allow a better prediction of responses and reduce unnecessary treatment
toxicity.
Study objective
The aim of this study is to evaluate the efficacy of a personalized drug
profiling method using short-term cultures of malignant cells derived from the
patient*s pleural fluid.
Study design
In this open label phase II study, the choice of second or third line therapy
will be determined by a personalized drug profiling method using short-term
cultures, of primary tumour cells.
Intervention
Pleural fluid that is drawn for symptom relief, will be used to isolate tumor
cells for short-term culture. A small scale drug screen will be performed
within 3 weeks after isolation of tumor cells. If sample tumor cells are
available, a large scale drug screen using the 101 anti-cancer compounds will
be performed as well. Based on the in vitro results, an advise on both single
agent and combination therapy will be provided by the committee of researchers.
The treating physician will decide whether single agent or combination therapy
is suitable for the patient and will determine which term therapy will be
started. Patients will be treated according to chemotherapy protocols that are
routinely used in our clinic and recorded in iProva. Response evaluation will
be done according to modified RECIST.
Study burden and risks
Pleural effusion is usually drawned for symptom relief. The patient therefore
don't need additional surgery. The collection of blood will - if possible - be
combined with a regular blood collection which is required for the treatment.
In about half of the patients it is not possible to do the test in the
laboratory. So there is no guarantee that there will be a treatment proposal on
the basis of the laboratory results. Furthermore, this research should show
whether the laboratory result is indeed a good predictor for what the best
follow-up treatment will be. So it is not sure if the predicted chemotherapy in
the patient will show result.
All patients may experience any side effects of chemotherapy.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
• Patients with histologically or cytologically proven malignant mesothelioma or non small cell lung cancer that have a pleural effusion;
• Age > 18 years;
• At the time of pleural fluid drainage, patients must have completed:
For MPM: at least first-line chemotherapy with a platinum (cisplatin or carboplatin) and pemetrexed combination.
For NSCLC: at least first and second line therapy according to the local guidelines.
• At the start of study treatment, patients must have documented evidence of progressive disease.
• Measurable or evaluable disease.
• 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:
o Hematology: Neutrophil count >= 1.5 x 109/l, Platelets >= 100 x 109/l, Hemoglobin >= 5.9 mmol/l.
o Hepatic function as defined by serum bilirubin <= 1.25 times the upper limit of normal (ULN), ALAT and ASAT <= 2.5 times the ULN, except for liver metastases then ALAT and ASAT < 5 times the ULN.
o 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, severe cardiac dysfunction or non-correctable bleeding tendency.
• Any identification of a driver mutation for which a registered treatment is available.
• Presence of symptomatic CNS metastases.
• Radiotherapy within 2 weeks prior to start of study treatment.
• Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition.
• Concomitant administration of any other experimental drugs under investigation.
• Any non-resolved grade 3 or higher toxicity.
• For neurotoxicity any non-resolved grade 2 or higher toxicity
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 | EUCTR2013-005621-24-NL |
| CCMO | NL47606.031.14 |