A study investigating the efficacy and safety of anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma.
- Conditions
- advanced or metastatic malignant pleural mesothelioma overexpressing mesothelinMedDRA version: 20.0Level: PTClassification code 10027406Term: MesotheliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003650-88-IT
- Lead Sponsor
- BAYER AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 248
1. Written informed consent for full study.
2. Histological documentation of MPM overexpressing mesothelin at the
moderate and stronger level in at least 30% of tumor cells as
determined by centrally performed IHC
Note: Patients with a sarcomatoid histology are not expected to have
mesothelin overexpression and should not be enrolled in the study.
3. Unresectable locally advanced or metastatic MPM after progression on
1st line treatment with platinum in combination with pemetrexed. Last
dose of previous therapy must be at least 28 days before start of study
treatment.
Note: Patients progressed on 1st line treatment with platinum plus
pemetrexed in combination bevacizumab are allowed
4. Patients must have at least 1 measurable lesion according to mRECIST
for mesothelioma i.e. pleural lesion(s) measured using mRECIST or
extra-pleural lesion(s) measurable per RECIST 1.1. This will be
confirmed by central review of images before the patient can be
randomized into the study.
Note: In case the only site of disease was previously treated with
radiotherapy, there should be evidence of unequivocal PD in this site:
measurable pleural disease should be assessed on a contrast enhanced
CT/MRI done at the minimum 4 weeks after the end of radiotherapy and
compared with previous imaging; unequivocal progression should be
judged by the investigator as per mRECIST per MPM
5. Age = 18 years (age limit may be higher if legally required in a
country e.g. in Japan adult age is considered > 20 years)
6. ECOG PS of 0 or 1
7. Life expectancy of at least 3 months
8. Women of childbearing potential (WOCBP) and men must agree to use
adequate contraception from signing of the ICF for full study until at
least 4 months after the last study drug administration. Men being
treated with vinorelbine are advised not to father a child during and up
to 6 months after treatment; for all male patients, prior to treatment
with either study drug, advice should be sought for conserving sperm
due to the chance of irreversible infertility as a consequence of
treatment (22).The investigator or a designated associate is requested
to advise the patient how to achieve an adequate birth control. Highly
effective (failure rate of less than 1% per year) contraception methods
(23) include: (...)
9. Adequate bone marrow, liver and renal function as assessed by the
following laboratory requirements conducted within 7 days before
starting study treatment:
• Total bilirubin < 1.5 x the upper limit of normal (ULN). Documented
Gilbert syndrome is allowed if total bilirubin is mildly elevated (< 6
mg/dL).
• ALT and AST < 3 x ULN (< 5 x ULN for patients with liver involvement
of their cancer).
• ALP limit < 2.5 x ULN (< 5 x ULN for patients with liver involvement of
their cancer).
• Amylase and lipase < 1.5 x ULN.
• Serum creatinine < 1.5 x ULN
• Glomerular filtration rate (GFR) = 30 mL/min/1.73 m2 according to
the Modification of Diet in Renal Disease (MDRD) abbreviated formula
• Adequate coagulation, as assessed by the following laboratory test
results:
o International normalized ratio (INR) or prothrombin time (PT) < 1.5 x
ULN (CTCAE Grade < 1) o Partial thromboplastin time (PTT) or activated PTT (aPTT) < 1.5 x ULN
(CTCAE Grade < 1)
Note: Patients on anti-coagulation therapy will be allowed to participate
if INR / PT and PTT / aPTT test results are compatible with the
acceptable benefit-risk ratio at the investigator's discretion
• Platelet (PLT) count > 100000/mm3 , without PLT transfusion w
1. Previous assignment to treatment during this study. Patients
permanently withdrawn from study participation will not be allowed to
re-enter the study.
2. Previous (within 5 drug half-lifes – if drug half-life in subjects is
known – or 28 days, whichever is shorther, before the start of study
treatment) or concomitant participation in another clinical study with
investigational medicinal product(s).
3. Close affiliation with the investigational site; e.g. a close relative of
the investigator, dependent person (e.g. employee or student of the
investigational site).
4. More than 1 previous systemic anti-cancer therapy line for MPM (even
if therapy used as neoadjuvant or adjuvant treatment).
Note: Patients pre-treated with systemic therapy other than platinum,
pemetrexed, bevacizumab (e.g. other cytotoxic drugs, immunotherapy,
targeted therapy, hormonal therapy, or any other experimental or
approved therapy or device) are not to be enrolled.
5. Patients with corneal epitheliopathy or any eye disorder that may
predispose the patients to this condition at the discretion of the
investigator in consultation with the ophthalmologist/optometrist.
Note: Low grades of superficial punctate keratitis, within the range seen
in the normal population, should not lead to the exclusion of the patient.
6. Previous or concurrent cancer that is distinct in primary site or
histology from mesothelioma within 5 years before randomization.
Exceptions: curatively treated
• Cervical cancer in situ.
• Non-melanoma skin cancer.
• Superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in
situ) and T1 (Tumor invades lamina propria)].
7. Major surgery, open biopsy or significant traumatic injury within 28
days before the start of study treatment.
8. Pregnant or breast-feeding patients. WOCBP must have a serum
pregnancy test performed a maximum of 7 days before the start of study
treatment, and a negative result must be documented before the start of
study treatment.
9. Pre-existing cardiac conditions as outlined below:
• Congestive heart failure > New York Heart Association (NYHA) class 2
• Unstable angina (angina symptoms at rest), new-onset angina (begun
within the last 3 months). Myocardial infarction less than 6 months
before the start of study treatment.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers
or digoxin are permitted).
10. Clinically significant uncontrolled hypertension (systolic bloodpressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal
medical management).
11. Arterial thrombotic or embolic events such as cerebrovascular
accident (including transient ischemic attacks), or venous pulmonary
embolism within 6 months before the start of study treatment; venous
thrombotic events as deep vein thrombosis within 3 months before the
start of study treatment.
12. Ongoing or active infection (bacterial, fungal, or viral) of NCI-CTCAE
version 4.03 Grade > 2.
13. Known history of human immunodeficiency virus (HIV) infection.
14. Known history of chronic hepatitis B or C.
15. Patients with seizure disorder requiring medication.
16. Brain metastases or meningeal tumors or other metastases in the
central nervous system (CNS). Patients with neurological symptoms
must undergo a contrast CT scan or MRI of the brain and/or other areas
of the CNS as applicable within 28 days before the start of study
treatment to exclude metastastic disease in the CNS.
17. History of organ allograft, stem cells or bone marrow transplant
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