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

Bayer

Status and phase: Completed; Phase 1

Conditions: Medical Oncology

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02824042

18329

2017-001978-42 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 1 patient group

Anetumab ravtansine

Experimental group

Description:

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.

Treatment:

Drug: Anetumab ravtansine (BAY94-9343)

Drug: Itraconazole