Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02824042
Recruitment Status : Completed
First Posted : July 6, 2016
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

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

Condition or disease Intervention/treatment Phase
Medical Oncology Drug: Anetumab ravtansine (BAY94-9343) Drug: Itraconazole Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Phase I Study to Assess the Effect of Itraconazole (CYP3A4 and P-gp Inhibitor) on the Pharmacokinetics of Anetumab Ravtansine and to Assess the ECG Effects, Safety and Immunogenicity of Anetumab Ravtansine Given as a Single Agent and Together With Itraconazole in Subjects With Mesothelin-expressing Advanced Solid Cancers
Actual Study Start Date : September 7, 2016
Actual Primary Completion Date : June 27, 2018
Actual Study Completion Date : August 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: 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)

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)




Primary Outcome Measures :
  1. PR interval duration [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  2. QRS interval duration [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  3. QT interval duration [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  4. Abnormal T/U waves [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  5. Heart rate [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  6. Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes [ Time Frame: 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 ]
  7. Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes [ Time Frame: 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 ]
  8. Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes [ Time Frame: 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 ]
  9. QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration [ Time Frame: Up to 2 months per patient ]
    ECG evaluation

  10. QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration [ Time Frame: Up to 2 months per patient ]
    ECG evaluation


Secondary Outcome Measures :
  1. Incidence of serious adverse events [ Time Frame: Up to 6 months per patient ]
  2. Incidence of non-serious adverse events [ Time Frame: Up to 6 months per patient ]
  3. Incidence of positive anti-drug antibody titer [ Time Frame: Up to 6 months per patient ]
  4. Incidence of neutralizing antibody titers [ Time Frame: Up to 6 months per patient ]
  5. Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study ]
  6. Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824042


Locations
Show Show 18 study locations
Sponsors and Collaborators
Bayer
Investigators
Layout table for investigator information
Study Director: Bayer Study Director Bayer
Additional Information:
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02824042    
Other Study ID Numbers: 18329
2017-001978-42 ( EudraCT Number )
First Posted: July 6, 2016    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Phase 1
Solid tumors
Mesothelin
Itraconazole
PK DDI
ECG thorough QTC
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Itraconazole
Maytansine
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators