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A Phase I Study to Assess the Safety, Pharmacokinetics, and Potential Effects of Amrubicin on the QT/QTc Interval in Cancer Patients With Advanced Solid Tumors.

Phase 1
18 Years
65 Years
Not Enrolling
Advanced Solid Tumors

Thank you

Trial Information

A Phase I Study to Assess the Safety, Pharmacokinetics, and Potential Effects of Amrubicin on the QT/QTc Interval in Cancer Patients With Advanced Solid Tumors.

Inclusion Criteria:

- Patients meeting all of the following criteria will be considered for enrollment into
the study:

1. Males or females, aged 18-65 years;

2. Histological or cytological diagnosis of solid malignancy for which no
acceptable standard therapy exists or for which approved standard therapy has

3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;

4. Life expectancy greater than 3 months;

5. Nonsmoker or not smoked or used tobacco products for at least 3 months before
the screening visit and agree to abstain from smoking/using tobacco products
throughout the formal study and until the End of Study visit;

6. Capable of giving informed consent, has signed the informed consent form, and is
willing to comply with scheduled visits, dose administration, and other study

7. Women of childbearing potential may participate, providing they have a negative
serum pregnancy test (β-HCG) at screening, and a negative urine pregnancy test
prior to dosing on Day 1 of each cycle;

8. Males and females of childbearing potential must agree to the use of at least 2
effective contraceptive methods until at least 28 days following the last dose
of study drug;

9. Serum potassium, magnesium and corrected calcium that is within institutional
normal range at screening;

10. Adequate organ function including the following:

- Adequate bone marrow reserve: absolute neutrophil count (segmented and
bands) (ANC) ≥1.5 x 109/L, platelet count ≥100 x 109/L, and hemoglobin ≥90

- Hepatic: bilirubin ≤1.5 x the upper limit of normal (ULN), ALT and AST ≤2.0
x ULN,

- Renal: serum creatinine ≤1.5 x ULN or calculated creatinine clearance >80

Exclusion Criteria:

- Patients meeting any of the following criteria will be excluded from the study:

1. Hypersensitivity to amrubicin or related compounds;

2. Radiotherapy with curative intent to a primary disease complex ≤ 28 days before
first dose; cranial radiotherapy ≤ 21 days before first dose; radiotherapy to
all other areas ≤ 7 days before first dose of amrubicin;

3. History or presence of clinically significant abnormal 12-lead ECG or triplicate
ECGs with a mean QT interval corrected for heart rate (HR) using Fridericia's
method (QTcF) of >450 msec (males) or >470 msec (females), a PR interval >240
msec or a QRS interval >110 msec (within 3 months of screening visit);

4. Left ventricular ejection fraction (LVEF) <50%;

5. Recent history (within 3 months of screening visit) of pericarditis and
pericardial effusion;

6. History within 6 months of the screening visit of one of the following:

- cardiac disease including congenital long-QT syndrome,

- angina, congestive heart failure,

- myocardial ischemia or infarction,

- myocarditis, chest pain or dyspnea on exertion of cardiac origin,,

- idiopathic or hypertrophic cardiomyopathy,

- sarcoidosis,

- syncope,

- epilepsy,

- or other clinically significant cardiac disease;

7. Family history of long QT syndrome;

8. Use of implantable pacemaker or implantable cardioverter defibrillator;

9. Clinically significant bradycardia (<50 beats per minute);

10. Systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg;

11. Previous treatment with an investigational agent or any anticancer therapy
within 4 weeks prior to the 'off-drug' visit;

12. Previous treatment with anticancer therapy and has not fully recovered (Common
Terminology Criteria Adverse Event [CTCAE] Grade 1, except alopecia) from the
toxic effects of that treatment;

13. Treatment with any medication known to produce QT prolongation enzyme-inducing
anticonvulsants, non-prescription medications including topical medications, all
vitamins, minerals, herbs or dietary supplements/remedies (e.g., Saint John's
Wort or Milk Thistle) for at least 7 days before the start of the off-drug

14. Previous treatment with any anthracycline;

15. Any condition that would put the patient at undue risk or discomfort as a result
of adherence to study procedures;

16. Women who are pregnant or nursing;

17. Uncontrolled intercurrent illness such as myelosuppression, renal impairment,
hepatic impairment, infection and uncontrolled diabetes;

18. Symptomatic central nervous system metastases. Patients with asymptomatic brain
metastases are allowed. The patient must be stable for ≥ 2 weeks after
radiotherapy, if the patient is on corticosteroids, the dose of corticosteroids
must have been stable for ≥ 2 weeks prior to the first dose of study treatment,
or be in the process of being tapered;

19. Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis
not related to prior treatment;

20. History of seropositive HIV or patients who are receiving immunosuppressive or
myelosuppressive medications that would, in the opinion of the investigator,
increase the risk of serious neutropenic complications;

21. Positive urine drug screen for undeclared concomitant medications and/or illegal
drug use at screening.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To characterize the pharmacokinetics of amrubicin and amrubicinol (metabolite) in plasma, whole blood, and urine in patients given amrubicin as 5 minute IV infusions at 40 mg/m2 for 3 consecutive days; data will be obtained from blood & urine samples

Outcome Description:

The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment.

Outcome Time Frame:

Cycle 1: all primary outcome measures are collected during the first 21 days.

Safety Issue:


Principal Investigator

Markus Renschler, MD

Investigator Role:

Study Director

Investigator Affiliation:

Celgene Corporation


United States: Food and Drug Administration

Study ID:

AMR PH US 2008 PK002



Start Date:

June 2009

Completion Date:

May 2011

Related Keywords:

  • Advanced Solid Tumors
  • Neoplasms



James Graham Brown Cancer Center Louisville, Kentucky  40202
Montefiore Medical Center Bronx, New York  10467-2490
University of California San Diego La Jolla, California  92093
Indiana University Cancer Pavilion Indianapolis, Indiana  46202
Hunstman Cancer Institute Salt Lake City, Utah  84112
Sarcoma Oncology Center Santa Monica, California  90403
Sinai Hospital of Baltimore- Alvin and Lois Lapidus Cancer Institute Baltimore, Maryland  21215
UT Health Science Center at San Antonio- Cancer Therapy and Research Center San Antonio, Texas  78229