Study of Hsp90 Inhibitor, STA-9090 for Relapsed or Refractory Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: STA-9090
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hsp90 Inhibitor; relapsed; refractory

Summary:

      Small cell lung cancer (SCLC) is a chemotherapy and radiotherapy sensitive tumor, but with
      very high rates of relapse and metastasis, resulting in a very poor outcome. Among
      limited-stage patients, the relapse rate is at least 80% and among extensive-stage patients,
      the relapse rate is 95-98%. The impetus to develop more effective therapies against novel
      targets in SCLC is therefore high.

      Hsp-90 inhibitors are a new class of drugs with important anti-malignant potential in a
      variety of tumor types because of the reliance of multiple oncoproteins on Hsp90 function.
      Although small cell neuroendocrine tumors generally carry many mutated oncoproteins, without
      clearly defined clients for Hsp90 mediating inhibitor effects in these cells, a recent study
      demonstrated that Hsp90 inhibition causes massive apoptosis by activating the intrinsic
      apoptotic pathway in a number of SCLC cell lines. SCLC is a particularly attractive target
      for apoptosis inducing drugs because of high growth rates and evidence of molecular
      alterations affecting apoptotic mechanisms.

      STA-9090 is a novel, small-molecule inhibitor of Hsp90. Unlike earlier generations of Hsp90
      inhibitors, STA-9090 has been shown to be a potent inducer of apoptosis in a variety of cell
      lines and has anti-tumor activity in multiple types of human xenografts. As was seen with
      other Hsp90 inhibitors, STA-9090 also induces apoptosis in a number of SCLC cell lines.

      Based on the anti-tumor potential seen pre-clinically with Hsp90 inhibition, the potent
      effects of STA-9090 seen pre-clinically as compared with other inhibitors in the same class,
      as well as early data suggesting safety and tolerability of this drug in the Phase I setting,
      we propose to study the single-agent activity of STA-9090 in a Phase II trial of patients
      with relapsed or refractory small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of small cell lung cancer and confirmed progressive
             disease by radiographic study

          -  </= 3 prior chemotherapy regimens

          -  Subjects with brain metastases will be allowed if they have been treated with surgery
             and/or radiation therapy > 21 days prior, are asymptomatic, and are stable for at
             least 1 week off steroids

          -  Must have measurable disease

          -  >/= 18 years of age

          -  Life expectancy of greater than 12 weeks

          -  EGOG performance status 0 or 1

          -  Lab values must be within limits outlined in the protocol

          -  Not pregnant or breastfeeding

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Chemotherapy or radiotherapy within 3 weeks or within 5 half-lives of previous therapy

          -  History of severe allergic or hypersensitivity reactions to taxanes.

          -  Subjects who have not recovered from adverse events or toxicities due to agents
             administered more than 4 weeks earlier to a grade 1 or less

          -  Not receiving any other study agents

          -  History of or current coronary artery disease, myocardial infarction, angina pectoris,
             angioplasty or coronary bypass surgery.

          -  Baseline QTc > 470 msec or previous history of QT prolongation while taking other
             medications.

          -  Ventricular ejection fraction of < 55%.

          -  History or current uncontrolled dysrhythmias, or requirement for antiarrhythmic
             medications, or Grade 2 or greater left bundle branch block.

          -  ECG with clinically significant ventricular arrhythmias or ischemia

          -  Major surgery within 4 weeks of starting treatment

          -  Poor venous access necessitating use of indwelling catheter for IV therapy

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance

          -  History of another malignancy unless disease-free for 3 years and deemed to be at low
             risk for recurrence