Pharmacokinetic and Safety Study of Pixantrone in Patients With Metastatic Cancer and Hepatic Impairment - Full Text View

Purpose

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).

Condition	Intervention	Phase
Metastatic Cancer	Drug: Pixantrone	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Non-randomized Cohort Study With Matched Controls Investigating Pharmacokinetic Parameters and Safety of a Single Dose of Pixantrone With Metastatic Cancer and Moderate, Severe, or No Hepatic Impairment.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Cell Therapeutics:

Primary Outcome Measures:

Pharmacokinetics [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
The following pharmacokinetic parameters will be calculated; CL, Cmax, AUC-Steady State, Tmax, T 1/2, AUCo-TLAST.

Secondary Outcome Measures:

Safety [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
All adverse events that occur during the study will be listed and the number of occurrences of each event will be calculated.

Estimated Enrollment:	32
Study Start Date:	May 2012
Estimated Study Completion Date:	February 2018
Estimated Primary Completion Date:	August 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Stage 1 -Moderate Hepatic Impairment Pixantrone	Drug: Pixantrone Experimental Drug
Experimental: Stage 2 - Severe Hepatic Impairment Pixantrone	Drug: Pixantrone Experimental Drug

Detailed Description:

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. Stage I will include patients with moderate hepatic impairment and Stage II will include patients with severe hepatic impairment. An analysis of data from the Stage I portion of the study will be performed to decide whether to enroll patients in the Stage II portion of the study. Patients with hepatic impairment (either moderate or severe) will be paired with matched control patients with normal hepatic function, matched on gender, age, and body surface are (BSA). Patients will receive a single dose of pixantrone on day 1 of a 21 day cycle. Blood samples will be obtained at various time points during the first week of the first cycle for pharmacokinetic (PK) analysis. If any patient with hepatic impairment develops a dose limiting toxicity, subsequent patients will be administered a lower dose of pixantrone. If any patient with hepatic impairment who is receiving the reduced dose of pixantrone experiences a dose limiting toxicity, the study will be terminated. Patients who demonstrate any clinical, radiologic, or other evidence of response or stabilization after the initial dose of pixantrone and who wish to continue treatment may do so at the discretion of the Investigator. Patients receiving additional cycles will be treated with pixantrone every 21 days for up to 5 additional cycles and will be followed for safety only, until 30 days after the last dose.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed Institutional Review Board (IRB) approved consent form
Age ≥ 18 years old
Histological confirmation of cancer from any previous cytological or tissue report
Diagnosis of metastatic disease based on biopsy, imaging, or clinical criteria
Failure of other antineoplastic therapies, or disease for which no standard therapy exists
At least 28 days since last antineoplastic therapy
ECOG PS ≤ 2 (see Appendix 8.2)
Life expectancy ≥ 12 weeks in Investigator's judgment
LVEF ≥ 50% by echocardiogram
Hemoglobin ≥ 8 g/dL (can be post transfusion)
Platelets ≥ 75 x 109/L
ANC > 1.5x109/L
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
Serum creatinine ≤ 1.0 x ULN
All acute toxicities related to prior treatment recovered to grade ≤ 1 or baseline except alopecia
Willingness and ability to comply with the visit schedule and assessments required by the study protocol
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:

Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m² according to the calculation index in Appendix 8.1
Total serum bilirubin > 4.0 ULN
LVEF < 50% by echocardiogram
Active grade 3/4 infection
Major surgery ≤ 28 days prior to first dose
Gilbert's syndrome
Known human immunodeficiency virus
Any antineoplastic therapy ≤ 28 days prior to first dose
New York Heart Association Classification III or IV heart disease (see Appendix 8.3)
Any contraindication or known allergy or hypersensitivity to the study drug
Pregnant or lactating
Concomitant therapy with anticancer agents (corticosteroid use is permitted)
Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study procedures or follow-up schedule
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01632436

Locations

United States, Texas
UTHSCSA-Cancer Therapy-Research Center
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Cell Therapeutics

Investigators

Principal Investigator:

John Sarantopoulos, MD

UTHSCSA- Cancer Therapy & Research Center

More Information

No publications provided

Responsible Party:	Cell Therapeutics
ClinicalTrials.gov Identifier:	NCT01632436 History of Changes
Other Study ID Numbers:	PIX 112
Study First Received:	June 27, 2012
Last Updated:	June 28, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cell Therapeutics:

Hepatic impairment
Metastatic Cancer

Additional relevant MeSH terms:

Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Liver Diseases
Neoplastic Processes
Pathologic Processes
Digestive System Diseases
Pixantrone

Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013