Doxorubicin Hydrochloride Liposome and Bortezomib in Treating Patients With Refractory Hematologic Cancer or Malignant Solid Tumor or Metastatic Breast Cancer

Exclusion Criteria

• •Phase II
• •Diagnosis of breast cancer
• •* Metastatic disease
• •Measurable disease by RECIST criteria
• •No symptomatic brain metastases
• •* Patients with treated brain metastases that have been stable for \> 3 months and does not require chronic steroids are eligible
• •Hormone receptor status not specified
• •PATIENT CHARACTERISTICS:
• •Phase I (closed to accrual as of 10/15/2007)
• •Karnofsky performance status 60-100%
• •Life expectancy ≥ 2 months
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •WBC ≥ 2,000/mm³
• •ANC ≥ 1,500/mm³ (≥ 1,000/mm³ for patients with marrow infiltration)
• •Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ for patients with marrow infiltration)
• •Hemoglobin ≥ 8 g/dL
• •Creatinine ≤ 2.5 mg/dL OR creatinine clearance ≥ 30 mL/min
• •AST and ALT \< 2.5 times upper limit of normal (ULN)
• •Total bilirubin \< 1.2 times ULN
• •Prothrombin time (PT) and activated partial thromboplastin time (aPTT) \< 1.5 times ULN
• •* Patients receiving warfarin or heparin therapy for a history of thrombosis, embolism, or other indication must have PT and/or aPTT within the accepted therapeutic ranges for those indications
• •Patients with a history of reactions to other liposomal drug formulations that are not due to the liposome itself may be eligible at the discretion of the investigator
• •No known HIV seropositivity
• •No known active hepatitis A, B, or C viral infection
• •No New York Heart Association class III or IV congestive heart failure
• •LVEF ≥ 45% by 2-D ECHO or MUGA
• •No acute ischemia or new conduction system abnormality by EKG
• •No conduction system abnormality (e.g., left bundle branch block) by EKG that would preclude the ability to detect new ischemic episodes
• •No myocardial infarction within the past 6 months
• •No significant comorbidity, such as poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that, in the opinion of the investigator, might compromise any aspect of the study
• •No uncontrolled infection
• •* Patients may have febrile episodes up to 38.5°C if these are felt to be due to tumor fever and the possibility of infection has been ruled out by evaluation
• •No prior hypersensitivity reaction to pegylated doxorubicin hydrochloride liposome or doxorubicin hydrochloride
• •* Patients with a history of reactions to other liposomal drug formulations and/or to the liposome itself, as opposed to the encapsulated agent, may be excluded at the discretion of the investigator
• •Phase II
• •Female or male
• •Menopausal status not specified
• •Karnofsky performance status 70-100%
• •Life expectancy ≥ 3 months
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception during and for 3 months after completion of study therapy
• •ANC ≥ 1,500/mm³
• •Platelet count ≥ 100,000/mm³
• •Hemoglobin ≥ 9.0 g/dL
• •Creatinine ≤ 2.5 mg/dL (≤ 200 µmol/L)
• •AST and ALT ≤ 2 times ULN
• •Alkaline phosphatase ≤ 2 times ULN (unless attributed to tumor)
• •Bilirubin ≤ ULN
• •Cardiac ejection fraction \> 50% by MUGA or 2-D ECHO
• •No clinical evidence of congestive heart failure
• •No New York Heart Association class II-IV cardiac disease
• •No myocardial infarction within the past 6 months
• •No uncontrolled angina
• •No severe uncontrolled ventricular arrhythmias
• •No evidence of acute ischemia or active conduction system abnormalities by EKG
• •* Any EKG abnormality at screening must be documented by the investigator as not medically relevant
• •No grade 2 peripheral neuropathy within the past 14 days
• •No significant comorbidity that would impair compliance with study therapy or interpretation of study results
• •No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of pegylated doxorubicin hydrochloride liposome
• •No hypersensitivity to bortezomib, boron, or mannitol
• •No serious medical or psychiatric illness likely to interfere with participation in this study
• •PRIOR CONCURRENT THERAPY:
• •Phase I (closed to accrual as of 10/15/2007)
• •More than 3 weeks since prior major surgery
• •More than 3 weeks since prior and no concurrent radiotherapy
• •More than 4 weeks since prior and no concurrent immunotherapy (i.e., interferon, interleukin, or other cytokine-based treatment)
• •More than 3 weeks since prior and no concurrent participation in another therapeutic clinical trial with an experimental drug
• •More than 3 weeks since prior and no other concurrent chemotherapy
• •No prior doxorubicin dose \> 400 mg/m²
• •No other concurrent antineoplastic therapy
• •Phase II
• •More than 6 months since prior anthracyclines
• •More than 14 days since other prior investigational drugs
• •No more than 300 mg/m² of prior doxorubicin or 540 mg/m² of prior epirubicin
• •No more than two prior chemotherapy regimens for metastatic disease
• •No other concurrent antineoplastic therapy