Clinical and Translational Study of STA-9090
Condition: Colon Cancer; Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms
Intervention: STA-9090
Intervention description: Patients will be enrolled and receive 200mg/m2 of STA-9090. Patients will receive single agent STA-9090 intravenous (I.V.) infusion (an indwelling catheter may not be used) over 60 minutes weekly (three weeks on and one week off). Follow-up imaging will be performed every 8 weeks to evaluate response.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: STA-9090; colon; rectal; 10-029

Summary:

      The purpose of this study is to find out what effects, good and/or bad STA-9090 has on
      colorectal cancer. This is a phase II trial which tests both how well the drug works in
      fighting your cancer as well as any possible side effects it will have on the patient.

      Cancer is a disease of uncontrolled growth. This growth is controlled in part by a series of
      proteins that are part of a growth pathway. Some of these proteins are destroyed by a protein
      called HSP90 and STA-9090 is a test drug which blocks one of the proteins that helps cancer
      grow. This study will also look at molecular markers that may affect how the cancer grows,
      and how it responds to treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 metastases).

          -  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 participation.

          -  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).

        Exclusion Criteria:

          -  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
             administered.

          -  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
             enrollment.

          -  History of stroke within 6 months of treatment or other significant neurological
             limitations.

          -  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
             criterion 2.

          -  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
             diuretics

          -  Current or prior radiation therapy to the left hemithorax