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

Primary Purpose

Metastatic Cancer

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Pixantrone

About this trial

This is an interventional treatment trial for Metastatic Cancer focused on measuring Hepatic impairment, Metastatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UTHSCSA-Cancer Therapy-Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Stage 1 -Moderate Hepatic Impairment

Stage 2 - Severe Hepatic Impairment

Arm Description

Pixantrone

Outcomes

Primary Outcome Measures

Cmax

Cmax ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

Clearance

Clearance ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

AUC

AUCss ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

Secondary Outcome Measures

Incidence of Adverse Events

Safety and tolerability of pixantrone, including monitoring of adverse events (AEs); an AE is any untoward medical occurrence in a study subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage

Full Information

NCT ID

NCT01632436

First Posted

June 27, 2012

Last Updated

September 28, 2023

Sponsor

CTI BioPharma

1. Study Identification

Unique Protocol Identification Number

NCT01632436

Brief Title

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

Acronym

Hepatic

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.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Withdrawn

Why Stopped

No eligible patients enrolled

Study Start Date

May 2012 (undefined)

Primary Completion Date

August 2017 (Actual)

Study Completion Date

February 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CTI BioPharma

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Cancer

Keywords

Hepatic impairment, Metastatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stage 1 -Moderate Hepatic Impairment

Arm Type

Experimental

Arm Description

Pixantrone

Arm Title

Stage 2 - Severe Hepatic Impairment

Arm Type

Experimental

Arm Description

Pixantrone

Intervention Type

Drug

Intervention Name(s)

Pixantrone

Intervention Description

Experimental Drug

Primary Outcome Measure Information:

Title

Cmax

Description

Cmax ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

Time Frame

Day 1 Cmax

Title

Clearance

Description

Clearance ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

Time Frame

Day1-7

Title

AUC

Description

AUCss ratio of patients with hepatic impairment / matched control (geometric mean and 90% confidence interval)

Time Frame

Day 1-7

Secondary Outcome Measure Information:

Title

Incidence of Adverse Events

Description

Time Frame

Day 1-7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Sarantopoulos, MD

Organizational Affiliation

UTHSCSA- Cancer Therapy & Research Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UTHSCSA-Cancer Therapy-Research Center

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

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

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