Amrubicin has shown single-agent activity in lung cancer. The combination of cyclophosphamide and anthracyclines has been studied and concluded that the combination was tolerable, could be given safely, and therapeutically useful. This Phase I study will evaluate the combination of cyclophosphamide with amrubicin in relapsed solid tumors and will define the MTD of the combination in a US population.
OUTLINE: This is a multi-center study. This study will follow the 3+3 design with the following dose levels: * Dose Level -1: Amrubicin 20mg/m2, Cyclophosphamide 500mg/m2 * Dose Level 1: Amrubicin 25mg/m2, Cyclophosphamide 500mg/m2 * Dose Level 2: Amrubicin 30mg/m2, Cyclophosphamide 500mg/m2 * Dose Level 3: Amrubicin 35mg/m2, Cyclophosphamide 500mg/m2 * Dose Level 4: Amrubicin 40mg/m2, Cyclophosphamide 500mg/m2 Dose escalation starts from dose level 1. Amrubicin will be given as a slow IV push or infusion over approximately 5 minutes once daily for 3 consecutive days starting on day 1 of each 21 day cycle. Cyclophosphamide will be given at a fixed dose as an IV infusion over 30-60 minutes on day 1 of each 21 day cycle (following amrubicin). ECOG Performance Status: 0-1 Life expectancy: not specified Hematopoietic: * Hemoglobin (Hgb) \> 9 g/dL. * Platelets \> 100 K/mm3 * Absolute Neutrophil Count (ANC) \> 1.5 K/mm3 Hepatic: * Aspartate transaminase (AST) ≤ 2.5 x ULN * Alanine transaminase (ALT) ≤ 2.5 x ULN * Total bilirubin \< 1.5 x ULN Renal: * Calculated creatinine clearance ≥ 60cc/min Cardiovascular: * Left Ventricular Ejection Fraction (LVEF) ≥ LLN for institution within 60 days prior to registration for protocol therapy. * No history of cardiomyopathy or uncontrolled heart arrhythmia. Pulmonary: * No suspected, diffuse idiopathic interstitial lung disease or history of pulmonary fibrosis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
* Dose Level -1: 20mg/m2 * Dose Level 1: 25mg/m2 * Dose Level 2: 30mg/m2 * Dose Level 3: 35mg/m2 * Dose Level 4: 40mg/m2 Amrubicin will be given as a slow IV push or infusion over approximately 5 minutes once daily for 3 consecutive days starting on day 1 of each 21 day cycle.
Cyclophosphamide will be given at a fixed dose as 500mg/m2 IV infusion over 30-60 minutes on day 1 of each 21 day cycle (following amrubicin).
Highlands Oncology Group
Springdale, Arkansas, United States
Helen F. Graham Cancer Center
Newark, Delaware, United States
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.
Time frame: 24 months
To determine the toxicities of the combination of amrubicin and cyclophosphamide in patients with advanced solid tumors.
Time frame: 24 months
To assess response to the combination of amrubicin and cyclophosphamide
Time frame: 24 months
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Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
Medical Consultants, P.C.
Muncie, Indiana, United States
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States
Siteman Cancer Center
St Louis, Missouri, United States
Providence Portland Medical Center
Portland, Oregon, United States
Fox Chase Cancer Center Extramural Research Program
Rockledge, Pennsylvania, United States