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

DISEASE CHARACTERISTICS:

Phase I (closed to accrual as of 10/15/2007)

Histologically or cytologically confirmed solid tumor or hematologic malignancy, including, but not limited to, any of the following:

Breast cancer
Ovarian cancer
Myeloid or lymphoid leukemia
Hodgkin or non-Hodgkin lymphoma
Multiple myeloma
Measurable or evaluable disease

Must meet 1 of the following criteria:

Refractory to at least one prior conventional treatment regimen
Not a candidate for conventional therapy
No conventional therapy exists

No clinically or radiographically significant pleural or pericardial effusion

Patients with ascites may be eligible at the discretion of the investigator
Previously treated central nervous system disease allowed provided it has been stable for > 3 months and it is not the only site of measurable disease
Not eligible for a higher priority protocol

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