Pharmacokinetic and Safety Study of Pixantrone in Patients With Metastatic Cancer and Hepatic Impairment

• Status: Unknown status
• Trial end date: 2018-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will be conducted in patients with metastatic cancer and either moderate, severe, or no hepatic impairment who have failed other antineoplastic therapies or for whom there is no standard therapy. The study will be conducted in two stages. Using an existing pixantrone population pharmacokinetic (PPK) model, a model-based strategy will be used to evaluate the findings from the first stage of the study conducted in patients with moderate hepatic impairment and matched controls. The PPK evaluation will be completed prior to enrolling patients with severe hepatic impairment and additional matched controls during the second stage of the study. Patients with hepatic impairment will be paired with matched control patients with normal hepatic function, matched on gender, age, and body surface area (BSA).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CTI BioPharma
• Treatments: Pixantrone

Criteria

Inclusion Criteria:

1. Signed Institutional Review Board (IRB) approved consent form

2. Age ≥ 18 years old

3. Histological confirmation of cancer from any previous cytological or tissue report

4. Diagnosis of metastatic disease based on biopsy, imaging, or clinical criteria

5. Failure of other antineoplastic therapies, or disease for which no standard therapy exists

6. At least 28 days since last antineoplastic therapy

7. ECOG PS ≤ 2 (see Appendix 8.2)

8. Life expectancy ≥ 12 weeks in Investigator's judgment

9. LVEF ≥ 50% by echocardiogram

10. Hemoglobin ≥ 8 g/dL (can be post transfusion)

11. Platelets ≥ 75 x 109/L

12. ANC > 1.5x109/L

13. Stage I, moderate hepatic impairment: 1.5 < total serum bilirubin ≤ 3.0 ULN Stage II, severe hepatic impairment: 3.0 < total serum bilirubin < 4.0 ULN Stages I and II, normal liver function: total bilirubin < 1.0 ULN

14. Serum creatinine ≤ 1.0 x ULN

15. All acute toxicities related to prior treatment recovered to grade ≤ 1 or baseline except alopecia

16. Willingness and ability to comply with the visit schedule and assessments required by the study protocol

17. If fertile, both males and females must agree to use appropriate and effective contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the duration of study participation and for 6 months after last dose of study drug.

Exclusion Criteria:

1. Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m² according to the calculation index in Appendix 8.1

2. Total serum bilirubin > 4.0 ULN

3. LVEF < 50% by echocardiogram

4. Active grade 3/4 infection

5. Major surgery ≤ 28 days prior to first dose

6. Gilbert's syndrome

7. Known human immunodeficiency virus

8. Any antineoplastic therapy ≤ 28 days prior to first dose

9. New York Heart Association Classification III or IV heart disease (see Appendix 8.3)

10. Any contraindication or known allergy or hypersensitivity to the study drug

11. Pregnant or lactating

12. Concomitant therapy with anticancer agents (corticosteroid use is permitted)

13. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study procedures or follow-up schedule

14. Severe and/or uncontrolled medical disease that could compromise participation in the study or any medical or psychiatric condition that in the opinion of the Investigator would make study drug administration hazardous or obscure the interpretation of data