A Phase II Clinical and Translational Study of STA-9090 in Patients With Refractory Metastatic Colorectal Cancer
- The patient has histologically or cytologically-confirmed colorectal cancer with
metastatic disease documented on diagnostic imaging studies.
- The patient has measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded),
measuring ≥20 mm on conventional measurement techniques or ≥10 mm on spiral computed
tomography (CT) scan.
- The patient has received at least one prior standard and/or investigational regimen
for metastatic disease.
- The patient is age ≥18 years.
- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of
0-1 (Karnofsky≥ 80%).
- The patient has adequate hematologic function as defined by an absolute neutrophil
count ≥1500/μL, hemoglobin ≥9/μdL, and a platelet count ≥100,000/μL.
- The patient has adequate hepatic function as defined by a total bilirubin ≤ 2.5x the
upper limit of normal (ULN), and aspartate transaminase (AST) and alanine
transaminase (ALT)≤3 x the ULN (or ≤5 x the ULN in the presence of known liver
- The patient, if not on anticoagulation, has adequate coagulation function as defined
by international normalized ratio (INR) ≤1.5 ULN and partial thromboplastin time
(PTT) ≤1.5x the ULN. Patients on full-dose anticoagulation must be on a stable dose
of oral anticoagulation or low molecular weight heparin, must have an INR value
within acceptable range for treatment and have no active bleeding or pathological
condition that, in the opinion of the investigator, carries a high risk of bleeding.
- The patient has adequate renal function as defined by serum creatinine ≤1.5 x the
institutional ULN or creatinine clearance ≥60 mL/min for patients with creatinine
levels above 1.5, as well as urine protein ≤1+ on routine analysis (if routine UA
indicates ≥2+ protein, a 24-hour urine collection for protein must demonstrate <
1000mg of protein in 24 hours to allow participation in the study).
- The patient has a life expectancy of > 3 months.
- Because the teratogenicity of STA-9090 is not known, men and women of childbearing
potential must agree to use adequate contraception (hormonal or barrier birth
control; abstinence) prior to study entry and for the duration of study
- The patient has the ability to read and willingness to sign informed consent.
- For stage I of the protocol (the first 15 patients) the tumor must be amenable to
biopsy and the patient must be willing to undergo pre and post treatment biopsies.
- The patient must have a normal QTc interval on baseline ECG , (<470 milliseconds,
males and females).
- Patient may not have received chemotherapy within 4 weeks prior to entering the
study, and must have recovered (to grade 1 or less) from adverse events due to agents
- Primary brain tumors or active brain metastases. However, patients with a history of
CNS metastases will be eligible if they have been treated and are stable for 4 weeks
after completion of treatment, with image documentation required, and must be either
off steroids or on a stable dose of steroids for a minimum of 2 weeks prior to
- History of stroke within 6 months of treatment or other significant neurological
- Major surgery within 4 weeks prior to entering the study.
- Poor venous access for study drug administration or would require a peripheral or
central indwelling catheter for study drug administration. Study drug administration
via indwelling catheters is prohibited at this time.
- Use of any investigational agents within 4 weeks prior to entering the study.
- History of severe allergic reactions to excipients (e.g., Polyethylene glycol 300 and
Polysorbate 80), including severe hypersensitivity reactions defined as ≥ Grade 3
based on NCI CTCAE version 3.
- Treatment with chronic immunosuppressants (e.g., cyclosporine following
transplantation or systemic steroids for treatment of autoimmune disease). However,
patients may receive steroids for stable CNS metastases as described in exclusion
- Uncontrolled intercurrent illness including, but not limited to, human
immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral
therapy, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations
that would limit compliance with study requirements.
- Other medications, or severe acute/chronic medical or psychiatric condition, or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration, or may interfere with the interpretation of study
results, and in the judgment of the investigator would make the patient inappropriate
for entry into this study.
- Ventricular ejection fraction (Ef) ≤ 45%.
- Inaccessible tissue for biopsy (first 15 patients only)
- History of or current coronary artery disease, myocardial infarction, angina
pectoris, angioplasty or coronary bypass surgery
- History of or current uncontrolled dysrhythmias, or requirement for antiarrhythmic
medications, or Grade 2 or greater left bundle branch block
- New York Heart Association class II/III/IV congestive heart failure with a history of
dyspnea, orthopnea or edema that requires current treatment with angiotensin
converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or
- Current or prior radiation therapy to the left hemithorax