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

NCT02824042 | Completed Phase 1 FDA Drug

• 2 other identifiers: 183292017-001978-42
• Study Type: interventional
• Target: 63
• Locations: 6 countries
• Sites: 18

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

Keywords

Phase 1; Solid tumors; Mesothelin; Itraconazole; PK DDI; ECG thorough QTC

Outcome Measures

Primary Outcomes (10)

• PR interval duration

  ECG evaluation

  Up to 2 months per patient

• QRS interval duration

  ECG evaluation

  Up to 2 months per patient

• QT interval duration

  ECG evaluation

  Up to 2 months per patient

• Abnormal T/U waves

  ECG evaluation

  Up to 2 months per patient

• Heart rate

  ECG evaluation

  Up to 2 months per patient

• Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes

  At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study

• Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes

  At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study

• Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes

  At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study

• QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration

  ECG evaluation

  Up to 2 months per patient

• QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration

  ECG evaluation

  Up to 2 months per patient

Secondary Outcomes (6)

• Incidence of serious adverse events

  Up to 6 months per patient

• Incidence of non-serious adverse events

  Up to 6 months per patient

• Incidence of positive anti-drug antibody titer

  Up to 6 months per patient

• Incidence of neutralizing antibody titers

  Up to 6 months per patient

• Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes

  At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study

Study Arms (1)

Anetumab ravtansine

EXPERIMENTAL

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.

Drug: Anetumab ravtansine (BAY94-9343); Drug: Itraconazole

Interventions

Anetumab ravtansine (BAY94-9343) 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)

Anetumab ravtansine

Itraconazole 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)

Anetumab ravtansine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:
• predominantly epithelial (≥50% tumor component) pleural or peritoneal mesothelioma
• epithelial ovarian cancer (fallopian tube and primary peritoneal cancers are eligible)
• adenocarcinoma of the pancreas,
• triple-negative adenocarcinoma of the breast
• non-small-cell adenocarcinoma of the lung
• gastric cancer (including gastro-esophageal junction)
• colon cancer
• cholangiocarcinoma
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (18)

UCLA-Santa Monica Medical Center

Santa Monica, California, 90404, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106-2602, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75230, United States

Location

Blacktown Cancer & Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

Epworth HealthCare

Richmond, Victoria, 3122, Australia

Location

CU Saint-Luc/UZ St-Luc

Bruxelles - Brussel, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

Centre Georges Francois Leclerc Dijon

Dijon, 21079, France

Location

Hôpital de la Timone - Marseille

Marseille, 13005, France

Location

Nederlands Kanker Instituut

Amsterdam, 1066 CX, Netherlands

Location

VUmc

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum St. Radboud

Nijmegen, 6525 GA, Netherlands

Location

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, 28040, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Related Links

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

MeSH Terms

Interventions

anetumab ravtansine; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: July 6, 2016
• Study Start: September 7, 2016
• Primary Completion: June 27, 2018
• Study Completion: August 5, 2019
• Last Updated: July 31, 2020

Record last verified: 2020-07

Locations

AU (2); FR (3); ES (3); NL (3); BE (2); US (5)