To investigate the feasibility of immediate P/D followed by cisplatin/pemetrexed chemotherapy (or carboplatin/pemetrexed chemotherapy) or deferred P/D after cisplatin/pemetrexed chemotherapy (or carboplatin/pemetrexed chemotherapy) in patients with…
ID
Source
Brief title
Condition
- Mesotheliomas
- Pleural disorders
- Respiratory tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary end-point
Rate of success to complete the full treatment (P/D + chemotherapy or
chemotherapy + P/D) within 20 weeks (± 2 weeks) after treatment start.
Treatment start is defined as day 1 of the first chemotherapy cycle in the
deferred surgery arm and the day of operation in the immediate surgery arm.
A patient is considered to be a *treatment success* if he/she meets all of the
following criteria:
1. Patient has received the full protocol treatment, defined as 3 cycles of
pemetrexed and cisplatin (allowing for the dose adjustments described in
section 5.3), preceded/followed by pleurectomy/decortication (P/D) (as
described in section 5.3).
2. Patient alive and has no evidence of progression/relapse at week 20 (±2
weeks) after the first day of starting protocol treatment (chemotherapy
followed by P/D or P/D followed by chemotherapy).
3. Patient has no persisting grade 3-4 treatment side-effects (CTCAE V 4.0) at
week 20 (±2 weeks) after the first day of starting protocol treatment
(chemotherapy followed by P/D or P/D followed by chemotherapy)
Secondary outcome
Secondary end-points
* Process indicators of the quality and uniformity of P/D and outcome: The
following measures were thought to ensure quality of surgery:
* Loco-regional failure free survival
* Progression free and overall survival.
* Treatment side-effects and perioperative mortality and morbidity at 30 and 90
days.
Background summary
The role of surgery in the treatment of malignant, pleural mesothelioma is
controversial. Concerning this subject, evidence in the form of randomized
controlled trials is scarce. There are two surgical options in treating
mesothelioma: pleurectomy/decortication (P/D) versus extra-pleural
pneumonectomy (EPP). Previously, patients standardly underwent the more
extensive surgery: the EPP. However, outcomes of (the less invasive) P/D seem
to be better than outcomes of EPP. Furthermore, survival outcomes of EPP are
known to be better when surgery is combined with chemotherapy. The combination
of P/D and chemotherapy has not yet been studied. However building on the
knowledge concerning EPP, a combination of P/D and chemotherapy could lead to
better survival outcomes, while also leading to less perioperative mortality
and morbidity.
In this study, the feasibility of the combination of P/D and chemotherapy is
assessed. More specifically: is it more feasible to treat mesothelioma with
chemotherapy in a neoadjuvant setting or is it more feasible to administer
chemotherapy postoperatively. The primary endpoint is the rate of successfully
completed treatments, surgically as well as chemotherapeutically; independent
of the order it is administered in and within 20 weeks of commencing said
treatment. Further endpoints include 20 week-survival, without signs of
progression, relapse or 'related adverse events' over grade 2 according to the
'Common Terminology Criteria for Adverse Events' (CTCAE). If patients progress
at any point before or during the three cycles of chemotherapy, this will be
considered as treatment failure. Further anti cancer treatment can only proceed
outside of the protocol. In the future, the results of this study can be used
to compare the combination of P/D and chemotherapy versus a combination of
chemotherapy and EPP or even no surgery as a control.
Study objective
To investigate the feasibility of immediate P/D followed by
cisplatin/pemetrexed chemotherapy (or carboplatin/pemetrexed chemotherapy) or
deferred P/D after cisplatin/pemetrexed chemotherapy (or carboplatin/pemetrexed
chemotherapy) in patients with early stage malignant pleural mesothelioma.
Study design
This is a multicenter, randomized, 1:1, non-comparative phase II trial.
Patients with early stage MPM will be randomized between
ARM A: immediate P/D followed by three cycles of chemotherapy (pemetrexed
500mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 as IV, both drugs given on
day 1, every three weeks) for non-progressing patients
ARM B: three cycles of chemotherapy (same regimen) followed by P/D, for
non-progressing patients.
Four weeks (±2 weeks) will be allowed between the baseline tumor assessment and
the start of treatment (surgery or chemotherapy).
Randomization should be done as soon as possible after baseline tumor
assessment.
Intervention
Surgery
The minimal *default* procedure to which all thoracic and oncological surgeons
participating in this trial will conform is *parietal and visceral pleurectomy
to macroscopically remove all tumor*.
Chemotherapy
On day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as IV
infusion over 10 minutes followed 30 minutes later by cisplatin 75 mg/m2 (or
carboplatin AUC 5) as IV over approximately 2 hours.
The three cycles of chemotherapy should start at four weeks (±2 weeks) after
baseline CT scan in the deferred surgery arm and at four weeks (min 3 - max 6
weeks) after surgery in the immediate surgery arm. Chemotherapy cycles are
defined as a 3 week period.
Study burden and risks
Patients participating in this study will not experience any extra risks. The
burden during participation in this study is low en mainly consists of standard
interventions and standard care. Six, standard outpatient visits wil take
place. The blood collection necessary for this study will be done during
regular blood collection, thus does not carry extra risk.
Avenue E. Mounier 83/11
Brussels 1200
BE
Avenue E. Mounier 83/11
Brussels 1200
BE
Listed location countries
Age
Inclusion criteria
1. Patients are aged 18 years or older, with pathologically proven malignant
pleural mesothelioma (MPM). All histological subtypes are accepted.
2. Stage cT1-3, N0-2, M0 according to UICC TNM classification. FDG-PET-CT scan
showing absence of M1, N3, supraclavicular and coeliac node involvement is
required. No clinical or radiological invasion of mediastinal structures
(heart, aorta, spine, esophagus, etc.) and no widespread chest wall invasion
(T4) are acceptable. Focal chest wall lesions are acceptable.
3. No prior treatment of any kind for mesothelioma is allowed, especially
prophylactic track irradiations after diagnostic procedures.
4. WHO performance status 0-1.
5. Fit to receive chemotherapy and undergo a P/D with optional removal of
hemidiaphragm and pericardium. The responsible surgeon and chest physician
should judge the required fitness prior to registration, taking into account
the results of all the relevant (i.e. pulmonary, cardiac) examinations.
6. No history of other malignancy within the last three years, except for
carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the
skin.
7. No pre-existing peripheral sensory or motor neuropathy > grade I according
to CTCAE v4.0.
8. No clinically significant pleural effusion that cannot be managed with
thoracentesis or pleurodesis (according to institutional practice). If
pleurodesis is considered, it should be done before randomization.
9. No significant cardiovascular morbidity (assessed by cardiologist)
precluding surgery.
10. Adequate organ function, evidenced by the following laboratory results
within two weeks (+/- 3 days) prior to randomization with a buffer range from
the normal values of +/- 5% for hematology and +/- 10% for biochemistry [with
the EXCEPTION of Glomerular Filtration Rate] are acceptable):
*absolute neutrophil count >1500/l;
*Platelet count >100,000/l;
*Hemoglobin >11.0g/dL or 7 mmol/L;
*Total bilirubin <=1.5 upper limit of normal (ULN);
*SGOT (AST), SGPT (ALT), and alkaline phosphatase <=2.5×ULN;
*Glomerular Filtration Rate (GFR)>= 50 ml/min according to Cockcroft and Gault
Formula.
11. No current severe, uncontrolled systemic disease (e.g., clinically
significant cardiovascular, pulmonary, or metabolic disease, wound healing
disorders; ulcers; or bone fractures, known infection with HIV, active
hepatitis B and/or hepatitis C virus).
12. No major surgical procedure or significant traumatic injury within 28 days
prior to randomization or anticipation of the need for major surgery (other
than P/D) during the course of study treatment.
13. No history of receiving any investigational treatment within 28 days of
randomization.
14. No known hypersensitivity to pemetrexed or cisplatin or carboplatin or
their components.
15. Women of child bearing potential (WOCBP) must have a negative serum (or
urine) pregnancy test within 3 days prior to the start of chemotherapy/surgery.
Patients of childbearing/reproductive potential should use adequate birth
control measures, as defined by the investigator, during the study treatment
period and for at least three months after the last study treatment. A highly
effective method of birth control is defined as those which result in low
failure rate (i.e. less than 1% per year) when used consistently and correctly.
Female subjects who are breast feeding should discontinue nursing prior to the
start of chemotherapy/surgery and until three months after the last study
treatment.
16. Absence of any psychological, familial, sociological or geographical
donation potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before
registration in the trial. Absence of any other inability or unwillingness to
comply with the requirements of the protocol as assessed by the investigator.
17. Before patient registration written informed consent must be given
according to ICH/GCP, and national/local regulations.
Exclusion criteria
Mentioned earlier (inclusion criteria).
Design
Recruitment
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 |
|---|---|
| ClinicalTrials.gov | NCT02436733 |
| CCMO | NL59830.078.17 |