The main purpose of this study is to assess whether the study drug anetumab ravtansine is more effective than treatment with vinorelbine in patients with stage IV, mesothelin overexpressing malignant pleural mesothelioma. Efficacy will be measured…
ID
Source
Brief title
Condition
- Mesotheliomas
- Pleural disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess whether the study drug anetumab ravtansine is more effective than
treatment with vinorelbine in patients with stage IV, mesothelin
overexpressing malignant pleural mesothelioma measured by evaluating the
progression free survival.
Secondary outcome
The secondary endpoints are overall survival, patient-reported outcomes, other
efficacy parameters and safety. Other endpoints are evaluating the
pharmacokinetics and biomarkers.
Background summary
Malignant pleural mesothelioma (MPM) is a locally invasive, usually fatal
neoplasm arising from the mesothelial surfaces of the pleural cavity with a
median life expectancy of approximately 1 year following diagnosis. Currently,
there is no standard of care for second line therapy following a platinum based
treatment. Anetumab ravtansine is an antibody-drug conjugate (ADC) targeting
mesothelin which has demonstrated
favorable safety profile and improvement in objective response rate in
preclinical and phase I studies in advanced, unresectable or metastatic
epithelial mesothelioma. Such responses would translate to the potential for
anetumab ravtansine to impart clinical benefit as the 2nd line treatment for
advanced mesothelioma which represents an indication of high unmet medical need
for effective treatment options.
Study objective
The main purpose of this study is to assess whether the study drug anetumab
ravtansine is more effective than treatment with vinorelbine in patients with
stage IV, mesothelin overexpressing malignant pleural mesothelioma. Efficacy
will be measured by evaluating the progression
free survival from randomization along with other indicators of tumor response.
The safety of the study drug will also be investigated as well as overall
survival. Further objectives are to evaluate the pharmacokinetics, anti-drug
antibodies and biomarkers as well as Patient reported outcomes.
Study design
A randomized, open-label, active-controlled, two-arm, multicenter, phase II
trial. patients will be randomly assigned in a 2:1 ratio to receive anetumab
ravtansine or vinorelbine.
Intervention
Starting dose 6.5 mg / kg mg anetumab ravtansine intravenously once every three
weeks compared with weekly intravenous infusion of 30 mg / m2 vinorelbine.
Study burden and risks
Each patient will undergo a pre-screening visit for testing mesothelin
over-expression; in some cases, a new biopsy should be obtained for this
purpose.
Examination including eye examination, 2 patient questionnaires, ECG and tumor
assessments will be performed at specific visits.
Participation in the study will involve weekly or three weekly visits with
blood tests (3-29 mL) and physical exams (full or brief).
Visits will continue until the disease progresses, further follow up will be
done via 3 monthly telephone contacts
Anetumab ravtansine may have a therapeutic benefit, this can*t be guaranteed.
Patients are at risk of side effects.
Most common anticipated risks associated with anetumab ravtansine are nausea,
fatigue, vomiting, anorexia, diarrhea, peripheral neuropathy, increased Alanine
aminotransferase (ALT) and Aspartate aminotransferase (AST) and eye toxicity.
Most common anticipated risks associated with vinorelbine are neutropenia, loss
of some reflex reactions, constipation, nausea, vomiting, diarrhea, abnormal
liver tests, alopecia, asthenia, fatigue, fever, erythema and local phlebitis.
Energieweg 1
Mijdrecht 3641RT
NL
Energieweg 1
Mijdrecht 3641RT
NL
Listed location countries
Age
Inclusion criteria
1. Histological documentation of malignant pleural mesothelioma (MPM) overexpressing mesothelin
2. Unresectable locally advanced or metastatic MPM after a locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.
3. Patients must have measurable disease
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
5. Life expectancy of at least 3 months
6. Adequate bone marrow, liver- and renal function
7. Left ventricular ejection fraction (LVEF) * 50% of the lower limit of normal (LLN) according to local institution ranges of normality.
Exclusion criteria
1. More than 1 previous systemic anti-cancer therapy line
2. Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the ophtalmologist
3. Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in the central nervous system (CNS).
4. Evidence of history of bleeding diasthesis.
5. Ongoing or active infection (bacterial, fungal, or viral) of National Cancer Institute*s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade > 2.
6. Pre-existing cardiac conditions
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 | EUCTR2012-003650-88-NL |
| CCMO | NL55311.078.15 |