Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Histologically-confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
Disease that is measurable and/ or evaluable by RECIST criteria. Patients with prostate cancer require presence of disease on bone scan and/or CT scan and evidence of increasing PSA after standard hormonal therapy
ECOG Performance Status ≤ 2
Life expectancy estimated to be at least 3 months

Acceptable liver function:

In the absence of disease involvement in the liver and if bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), AST (SGOT), ALT (SGPT) and GGT may be ≤ 2 times ULN
In the presence of disease involvement in the liver and if bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), AST (SGOT), ALT (SGPT) and GGT may be ≤ 5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN Patients with bone metastases alkaline phosphatases ≤ 5 times ULN

Acceptable renal function:

Serum creatinine ≤ 1.5 times ULN, OR
Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula)

Acceptable hematologic status:

Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
Hemoglobin ≥ 9 g/dL
Urinalysis with no evidence of proteinuria
Acceptable coagulation profile (PT or INR, PTT) < 1.5 times ULN
At least 4 weeks since prior chemotherapy or surgery, with recovery to Grade 1 or baseline of significant toxicities felt related to prior drug(s)
Women of childbearing potential must have a negative serum pregnancy test at screening.
All patients (males and females) of child-bearing potential must agree to use an effective method of birth control
Ability to understand and willingness to sign a written informed consent document
Patients with prostate cancer must continue androgen deprivation therapy with LHRH agonists

Exclusion Criteria:

Documentation of keratosis follicularis, also known as Darier or Darier-White disease
Known hypersensitivity to any study drug component, including thapsigargin derivatives, Polysorbate 20, or propylene glycol
Patients with known and untreated brain metastases. Patients with brain metastases that have been treated and demonstrated to be clinically stable for at least 30 days may be enrolled onto the study
Patients with a family history of coagulopathy or patients with DVT or pulmonary embolus within the last 6 months
Patients taking anti-coagulants that include Coumadin or low molecular weight heparin

Patients with pre-existing cardiac conditions:

Prior documented myocardial infarction within the last 6 months
Pre-existing cardiac failure (NYHA class III-IV)
Atrial fibrillation on anti-coagulants
Unstable angina
Severe valvulopathy
Cardiac angioplasty or stenting within the last 6 months
Use or requirement for use of inhibitors or inducers of cytochrome isoenzymes
Corrected QTc prolongation value, calculated using Bazett's formula (QTcB = QT/RR ½), > 450 msec
Pregnant or lactating females
Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
Active uncontrolled infection, including known history of AIDS or hepatitis B or C
Any psychological, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
Concurrently receiving any other investigational agents while on study