A study investigating the efficacy and safety of anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma.

Phase 1

• Conditions: Patients with advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin; MedDRA version: 20.0 Level: LLT Classification code 10035605 Term: Pleural mesothelioma malignant advanced System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003650-88-GB
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-21
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 210

Inclusion Criteria

Eligibility criteria for mesothelin expression testing:
1. Written informed consent for mesothelin expression testing.
2. Unresectable locally advanced or metastatic MPM, confirmed by histology.
3. Availability of archival or fresh tissue for testing of mesothelin expression level.
Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival tissue is available and if in the investigator’s judgement, there is no additional risk for the patient’s safety. Patients with a sarcomatoid histology are not expected to have mesothelin overexpression and should not be enrolled in the study.
4. Age = 18 years (age limit may be higher if legally required in a country e.g. in Japan adult age is considered = 20 years).
5. ECOG PS of 0 or 1 (specified in Section 16.1).
6. Life expectancy of at least 3 months.
7. No prior treatment with anetumab ravtansine or vinorelbine.
8. No prior use of targeted agents, experimental therapy or systemic anti-cancer treatment other than ongoing or completed 1st line platinum/pemetrexed (with or without bevacizumab).

Eligibility criteria for study treatment
1. Written informed consent for full study.
2. Histological documentation of MPM overexpressing mesothelin at the moderate and stronger membrane staining level in at least 30% of viable tumor cells as determined by centrally performed IHC.
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 RECIST1.1. This will be confirmed by central review of images before the patient can be randomized into the study
5. ECOG PS of 0 or 1
6. Life expectancy of at least 3 months
7. Women of childbearing potential (WOCBP) and fertile 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. 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 to be used (combined hormonal contraception, IUD, bilateral tubal occlusion or vasectomised partner or sexual abstinence).
Male patients with a female partner of childbearing potential must use a condom and ensure that an additional form of contraception is also used during treatment and until 4 months after last study drug administration.
8. 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

Exclusion Criteria

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 blood pressure > 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified