A PHASE II/III RANDOMIZED STUDY OF PEMBROLIZUMABIN PATIENTS WITH ADVANCED MALIGNANT PLEURAL MESOTHELIOMA
- Conditions
- PATIENTS WITH ADVANCED MALIGNANT PLEURAL MESOTHELIOMAMedDRA version: 22.1Level: LLTClassification code 10051930Term: Mesothelioma malignancy unspecifiedSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002286-60-IT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 520
Eligibility Criteria
There will be NO EXCEPTIONS to eligibility requirements at the time of randomization. Questions about eligibility criteria should be addressed prior to randomization.
The eligibility criteria for this study have been carefully considered. Eligibility criteria are standards used to ensure that patients who enter this study are medically appropriate candidates for this therapy. For the safety of the patients, as well as to ensure that the results of this study can be useful for making treatment decisions regarding other patients with similar diseases, it is important that no exceptions be made to these criteria for admission to the study.
Patients must fulfill all of the following criteria to be eligible for admission to the study:
4.1.1Patients must have histologically confirmed malignant pleural mesothelioma. Patients must be eligible to receive standard chemotherapy with pemetrexed and cisplatin and have no contraindications to standard chemotherapy.
4.1.2Patients must have unresectable advanced and/or metastatic disease, incurable by standard therapies.
4.1.3All patients must have a cellular tumour block from their primary or metastatic tumour available and consent to release the block/recently cut slides for correlative analyses (See Section 11.0) and the centre/pathologist must have agreed to the submission of the specimen(s).
4.1.4Presence of radiologically documented disease. At least one site of disease must be unidimensionally measurable* by mRECIST or RECIST 1.1 (see Section 8.0) as follows:
CT scan (with slice thickness of = 5 mm) = 10 mm ¿longest diameter
Physical exam (using calipers) = 10 mm
Lymph nodes by CT scan = 15 mm ¿measured in short axis
Pleural rind as defined by Byrne et al [Byrne 2004].
*Consult CCTG if the patient does not have a measurable pleural rind; if RECIST 1.1 is used rather than mRECIST pleura is considered a non-target lesion and the patient may not be eligible.
All radiology studies must be performed within 21 days prior to registration (exception: within 28 days if negative).
4.1.5Age = 18 years.
4.1.6ECOG performance status 0 or 1.
4.1.7Previous Therapy
Cytotoxic Chemotherapy:
•Patients must not have received prior chemotherapy for any stage of advanced/metastatic disease.
•Patients who received previous (neo)adjuvant cisplatin-based systemic chemotherapy must have received the last dose of chemotherapy at least 12 months before registration. Please contact CCTG PRIOR to randomization for such patients.
Other Anti-Cancer Therapy:
•Patients may not have received targeted small molecule therapy, immunotherapies and viral therapies, biologic therapies and angiogenesis inhibitors for advanced/metastatic disease, or any prior immunotherapy for any stage of disease.
Radiation:
Patients may have had prior radiation therapy, but NOT to the thorax unless clear disease progression has been demonstrated and confirmed with CCTG. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study. Radiation must have involved < 30% of functioning bone marrow and there must be measurable disease outside the previously irradiated area (patients whose sole site of disease (for example pleural rind) is in a previously irradiated area are ineligible UNLESS there is evidence of progression, or new lesions have been documented, in the irradiated field). (Exceptions may be made however, for low dose, palliative radiotherap
Patients who fulfill any of the following criteria are not eligible for admission to the study:
1.Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
2. Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3. Must not have received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed.
4. Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
5. Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction ( including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or who have had unstable angina congestive heart failure or myocardial infarction within the previous year. Patients with a significant cardiac history, this includes hypertension, even if controlled, should have a LVEF = 50%.
6. Patients with a history of other malignancies requiring concurrent anticancer therapy.
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or any of the other chemotherapy agents.
8. Patients receiving concurrent treatment with other anti-cancer therapy or other investigational anti-cancer agents.
9. Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
• Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) [note: testing in asymptomatic patients is not required] or tuberculosis).
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Any other medical conditions that might be aggravated by treatment.
• Serious or non-healing wound, ulcer, or bone fracture.
10 Patients with evidence of interstitial lung disease.
11. Pregnant or lactating women. (N.B.: All women of childbearing potential must have a negative pregnancy test within 72 hours prior to registration).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method