Thorough ECG (Electrocardiogram) and Drug Interaction Study With Anetumab Ravtansine and Itraconazole

NCT ID: NCT02824042

Last Updated: 2020-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-07
• Study Completion Date: 2019-08-05

Brief Summary

Characterize the safety, tolerability, ECG effects, pharmacokinetics and immunogenicity of anetumab ravtansine given as single agent and after inhibition of CYP3A4 and P-gp by concomitant administration of itraconazole in subjects with mesothelin-expressing advanced solid cancers

Conditions

Medical Oncology

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anetumab ravtansine

The evaluation of multiple ECG parameters and the drug-drug interaction (DDI) potential of anetumab ravtansine parameters when administered alone and together with itraconazole 100 mg oral capsules will be conducted in 2 sequential parts. On Cycle 1 Day 1, anetumab ravtansine will be given alone at a dose of 6.5 mg/kg in Part 1 and Part 2. On Cycle 2 Day 1, anetumab ravtansine will be given together with itraconazole at a dose of 0.6 mg/kg in Part 1, and at a dose of 6.5 mg/kg (planned) in Part 2.

Group Type: EXPERIMENTAL

Anetumab ravtansine (BAY94-9343)

Intervention Type: DRUG

Anetumab ravtansine given IV On Day 1 of each 21-day treatment cycle Part 1: Cycle 1 Day 1: 6.5 mg/kg of body weight (BW) Cycle 2 Day 1: 0.6 mg/kg BW Part 2: Cycle 1 Day 1: 6.5 mg/kg BW Cycle 2 Day 1: 6.5 mg/kg BW (planned dose) Continuous treatment: Cycles ≥3 Day 1: 6.5 mg/kg BW once every 3 weeks (Q3W)

Itraconazole

Intervention Type: DRUG

Itraconazole 100 mg oral capsules given by mouth Cycle 1 (Day 18): 200 mg twice daily (BID) (Days 19 - 21): 200 mg once daily (QD) Cycle 2 (Days 1-8): 200 mg QD 12 days in total (Part 1 or Part 2)

Interventions

Anetumab ravtansine (BAY94-9343)

Anetumab ravtansine given IV On Day 1 of each 21-day treatment cycle Part 1: Cycle 1 Day 1: 6.5 mg/kg of body weight (BW) Cycle 2 Day 1: 0.6 mg/kg BW Part 2: Cycle 1 Day 1: 6.5 mg/kg BW Cycle 2 Day 1: 6.5 mg/kg BW (planned dose) Continuous treatment: Cycles ≥3 Day 1: 6.5 mg/kg BW once every 3 weeks (Q3W)

Intervention Type: DRUG

Itraconazole

Itraconazole 100 mg oral capsules given by mouth Cycle 1 (Day 18): 200 mg twice daily (BID) (Days 19 - 21): 200 mg once daily (QD) Cycle 2 (Days 1-8): 200 mg QD 12 days in total (Part 1 or Part 2)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:

1. predominantly epithelial (≥50% tumor component) pleural or peritoneal mesothelioma

2. epithelial ovarian cancer (fallopian tube and primary peritoneal cancers are eligible)

3. adenocarcinoma of the pancreas,

4. triple-negative adenocarcinoma of the breast

5. non-small-cell adenocarcinoma of the lung

6. gastric cancer (including gastro-esophageal junction)

7. colon cancer

8. cholangiocarcinoma

9. Thymic carcinoma

• Subjects must have no standard therapy available, or have actively refused standard therapy
• Subjects must provide samples of archival tumor tissue collected and submitted anytime during the study
• Subjects must have a life expectancy of at least 12 weeks
• Subjects must have ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
• Subjects must have adequate bone marrow, renal and hepatic function and coagulation
• Subjects must have normal or clinically insignificant ECG at screening
• Women of reproductive potential must have a negative serum pregnancy test obtained within 3 days before the start of anetumab ravtansine
• Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active. This applies from the time period between signing of the informed consent until at least 6 months after the last administration of the last study drug. 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 6 months after last study drug administration.

Exclusion Criteria

• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial noninvasive bladder tumors or any previous cancer curatively treated ≥ 3 years before the start of anetumab ravtansine
• New or progressive brain or meningeal or spinal metastases
• Corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy, or may interfere with diagnosis of treatment-emergent corneal epitheliopathy at the ophthalmologist's or the investigator's discretion
• History or current evidence of

• biliary cirrhosis
• malignant biliary obstruction unless the bile flow to the gastrointestinal tract is maintained by a fully operational biliary stent
• CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 bleeding disorder within 4 weeks before the start of anetumab ravtansine
• uncontrolled cardiovascular disease or uncontrolled hypertension
• Long QT Syndrome
• HIV infection
• Hepatitis B or C infection
• Had a major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine
• Had solid organ or bone marrow transplantation
• Have LVEF (left ventricular ejection fraction) <50% at screening
• Have QTc >450 ms or heart rate ≥100 bpm or ≤45 bpm at screening
• Poor CYP2D6 metabolizers based on the screening test for genetic polymorphisms in CYP2D6 metabolizing capacity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

UCLA-Santa Monica Medical Center

Santa Monica, California, United States

Henry Ford Health System

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Mary Crowley Medical Research Center

Dallas, Texas, United States

Blacktown Cancer & Haematology Centre

Blacktown, New South Wales, Australia

Epworth HealthCare

Richmond, Victoria, Australia

CU Saint-Luc/UZ St-Luc

Bruxelles - Brussel, , Belgium

UZ Gent

Ghent, , Belgium

Hôpital Henri Mondor

Créteil, , France

Centre Georges Francois Leclerc Dijon

Dijon, , France

Hôpital de la Timone - Marseille

Marseille, , France

Nederlands Kanker Instituut

Amsterdam, , Netherlands

VUmc

Amsterdam, , Netherlands

Universitair Medisch Centrum St. Radboud

Nijmegen, , Netherlands

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, , Spain

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Countries

United States; Australia; Belgium; France; Netherlands; Spain

Related Links

https://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Other Identifiers

2017-001978-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18329

Identifier Type: -

Identifier Source: org_study_id