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Completed

NCT Number: NCT02824042

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

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

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Key information

Conditions

Medical Oncology

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Blacktown Cancer & Haematology Centre, Blacktown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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

Treatment and study plan

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)

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)

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Jul 6, 2016
Registry last updated
Jul 31, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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