Clinical Trials /

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

NCT02824042

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Lung Adenocarcinoma
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Peritoneal Mesothelioma
  • Pleural Mesothelioma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:Thorough ECG (Electrocardiogram) and Drug Interaction Study With Anetumab Ravtansine and Itraconazole
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 18329
  • NCT ID: NCT02824042

Trial Conditions

  • Medical Oncology

Trial Interventions

DrugSynonymsArms
Anetumab ravtansine (BAY94-9343)Anetumab ravtansine
ItraconazoleAnetumab ravtansine

Trial Purpose

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

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Anetumab ravtansineExperimentalThe evaluation of the drug-drug interaction (DDI) potential of anetumab ravtansine 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.
  • Anetumab ravtansine (BAY94-9343)
  • Itraconazole

Eligibility Criteria

Inclusion Criteria:

- Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following 5 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

- Subjects must have no standard therapy available, or have actively refused standard therapy or, in the investigator's opinion, treatment in this study is clinically and ethically acceptable for the subject.

- Subjects must provide samples of archival tumor tissue collected any time before the general screening

- Subjects must have positive mesothelin expression in the archival tumor tissue, defined as the membrane intensity score of 1+, 2+ or 3+ (on the 0-3 scale) expressed on the membrane of ≥5% of tumor cells combined

- 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 7 days before the start of anetumab ravtansine

- Women and men of reproductive potential must agree to consistently use adequate contraception / birth control between signing of the informed consent and 60 days after the last administration of the last study drug. Female partners of childbearing potential from male subjects have to use adequate contraception / birth control between signing of the informed consent and 60 days after the last administration of the last study drug if the male is not sterilized.

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 requiring 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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:PR interval duration
Time Frame:Up to 6 months per patient
Safety Issue:Yes
Description:ECG evaluation

Secondary Outcome Measures

Measure:Incidence of serious adverse events
Time Frame:Up to 6 months per patient
Safety Issue:Yes
Description:
Measure:Incidence of non-serious adverse events
Time Frame:Up to 6 months per patient
Safety Issue:Yes
Description:
Measure:Incidence of positive anti-drug antibody titer
Time Frame:Up to 6 months per patient
Safety Issue:No
Description:
Measure:Incidence of neutralizing antibody titers
Time Frame:Up to 6 months per patient
Safety Issue:No
Description:
Measure: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 and 336h during cycle 3
Safety Issue:No
Description:
Measure: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 and 336h during cycle 3
Safety Issue:No
Description:

Trial Keywords

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