Influence of Ketoconazole on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer

NCT ID: NCT01324310

Last Updated: 2019-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-01
• Study Completion Date: 2012-01-01

Brief Summary

The purpose of this study is to evaluate the effect and safety of multiple doses of ketoconazole on the pharmacokinetics of romidepsin after a single intravenous (IV) infusion.

Conditions

Hematologic Malignancy; Malignant Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Romidepsin and ketoconazole

Romidepsin 8 mg/m^2 intravenous infused over 4 hours on Day 1 and Day 8.

Ketoconazole 400 mg oral once daily on Days 4-8

Group Type: EXPERIMENTAL

Romidepsin

Intervention Type: DRUG

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Ketoconazole

Intervention Type: DRUG

Ketoconazole 400 mg oral once daily on Days 4-8

Interventions

Romidepsin

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Intervention Type: DRUG

Ketoconazole

Ketoconazole 400 mg oral once daily on Days 4-8

Intervention Type: DRUG

Other Intervention Names

Istodax®, Romi, ROMI

Eligibility Criteria

Inclusion Criteria

1. Males and females 18 years of age or older at the time of signing the informed consent document.

2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Must have diagnosis of advanced malignancy and must have failed other available therapies considered standard of care for their disease.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

6. Negative urine or serum pregnancy test on females of childbearing potential; and

7. All females of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device [IUCD] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter. Female subjects should avoid the use of estrogen-containing contraceptives, since romidepsin may reduce the effectiveness of estrogen-containing contraceptives. An in vitro binding assay determined that romidepsin competes with β-estradiol for binding to estrogen receptors.

5. Concomitant use of drugs that may cause a significant prolongation of the corrected measurement of the time between the start of the cardiac Q wave and the end of the T wave (QTc).

6. Concomitant use of Cytochrome P 450 3A4 (CYP3A4) strong inhibitors within 1 week of trial medications.

7. Concomitant use of CYP3A4 strong inducers within 2 weeks of trial medications.

8. Concomitant use of therapeutic warfarin due to a potential drug interaction. Use of a low dose of warfarin or another anticoagulant to maintain patency of venous access port and cannulas is permitted.

9. Clinically significant active infection.

10. Known infection with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C.

11. Inadequate bone marrow or other organ function as evidenced by:

• Hemoglobin < 9 g/dL (transfusions and/or erythropoietin are permitted);
• Absolute neutrophil count (ANC) ≤ 1.0 * 10^9 cells/L [subjects with neutropenia (ANC 1-1.5) as a function of their disease may be supported with granulocyte-colony stimulating factor (G-CSF)];
• Platelet count < 100 * 10^9 cells/L or platelet count < 75 * 10^9 cells/L if bone marrow disease involvement is documented;
• Total bilirubin > 1.5 * upper limit of normal (ULN) or > 2.0 * ULN in the presence of demonstrable liver metastases;
• Serum aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) > 1.5 * ULN or > 2.0 * ULN in the presence of demonstrable liver metastases; or
• Serum creatinine > 2.0 * ULN;

12. Prior chemotherapy treatment within 3 weeks prior to the first day of romidepsin treatment (6 weeks for nitrosoureas) or prior treatment with an investigational agent within 4 weeks prior to the first day of romidepsin treatment.

13. Prior radiotherapy within 4 weeks prior to the first day of treatment. Subjects who have not fully recovered or whose acute toxicity related to prior radiotherapy has not returned to baseline are ineligible.

14. Major surgery within 2 weeks of study entry (day 1).

15. Concomitant use of any other anti-cancer therapy.

16. Concomitant use of any investigational agent.

17. Prior exposure to romidepsin (other histone deacetylase[HDAC] inhibitors are allowed).

18. Any known cardiac abnormalities, such as:

• Congenital long measure of the time between the start of the Q wave and the end of the T wave (QT) syndrome;
• . Mean QTc formula (QTcF) interval > 450 msec;
• A myocardial infarction within 12 months of study entry;
• A history of coronary artery disease (CAD), e.g., angina Canadian Class II-IV. A stress imaging study should be performed for any subject whose cardiac status is uncertain. If abnormal, an angiography should be completed to define whether or not CAD is present.
• An electrocardiogram (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of ≥ 2 mm, measured from isoelectric line to ST segment). A stress imaging study should be performed for any subject whose cardiac status is uncertain. If abnormal, an angiography should be completed to define whether or not CAD is present.
• Congestive Heart Failure (CHF) that meets the New York Heart Association (NYHA) Class II to IV definitions (see Appendix F) and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);
• A known history of sustained ventricular tachycardia(VT), ventricular fibrillation (VF), torsades de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
• Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above);
• Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 160/95; or
• Any cardiac arrhythmia requiring anti-arrhythmic medication

19. Subjects who are pregnant or breast-feeding.

Exclusion Criteria

1. Any significant medical condition or psychiatric illness that would prevent the subject from participating in the study.

2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

3. Subjects with significant gastrointestinal disease that may impair drug absorption, such as subjects with a history of Cohn's disease, colectomy, gastrectomy, celiac disease, or other diseases with known malabsorption.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ken Takeshita, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Florida Cancer Specialists

Sarasota, Florida, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Sarah Cannon Research UK

London, , United Kingdom

Countries

United States; United Kingdom

Other Identifiers

2010-022144-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ROMI-ADVM-001

Identifier Type: -

Identifier Source: org_study_id