A Double-blind Study Evaluating IPI-504 and Docetaxel in Patients With Non-Small Cell Lung Cancer

• Progression Free Survival [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To determine the progression free survival rate from randomization to progression or death whichever occurs first, of all patients and in a subpopulation of patients administered IPI-504 plus docetaxel versus placebo plus docetaxel
• Overall Response Rate [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To determine partial response or complete response occurring at any point post-treatment
• Time to Progression [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To identify the amount of time from randomization to progression, of all patients and in a subpopulation of patients administered IPI-504 plus docetaxel versus placebo plus docetaxel

• Progression Free Survival [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To determin the progression free survivial rate from randomization to progression or death whichever occurs first, of all patients and in a subpopulation of patients administered IPI-504 plus docetaxel versus placebo plus docetaxel
• Overall Response Rate [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To determine partial response or complete response occurring at any point post-treatment
• Time to Progression [ Time Frame: Up to three years from last patient study visit ] [ Designated as safety issue: No ]
  To identify the amount of time from randomization to progression, of all patients and in a subpopulation of patients administered IPI-504 plus docetaxel versus placebo plus docetaxel

The purpose of this study is to compare the impact of IPI-504 in combination with docetaxel to placebo in combination with docetaxel on life expectancy in patients with Non Small Cell Lung cancer (NSCLC). Docetaxel is an approved chemotherapy for NSCLC. An additional goal of the study is to determine the effect of IPI-504, in combination with docetaxel, verses placebo in, combination with docetaxel, on the growth of cancer

This is a Phase 2, double-blind, randomized, placebo-controlled study in patients with previously treated, locally advanced or metastatic Stage IIIb or IV NSCLC designed to compare IPI-504 plus docetaxel versus placebo plus docetaxel. All patients will have at least a 15 pack year smoking history. Tumor samples will be assessed by a central pathology reviewer to confirm pathology that is documented at baseline; this review need not occur in advance of randomization.

• Drug: IPI 504 plus Docetaxel

  450 mg/m2 (starting dose) IPI-504 or placebo IV (in the vein) day 1, 8 & 15 during each 21 day cycle

  75 mg/m2 in US and EU, 60 mg/m2 in South Korea and Taiwan Docetaxel (Taxotere®) will be administered by IV infusion every 3 weeks (Day 1 of each 21-day cycle)

  Other Names:

  • IPI-504
  • Docetaxel
• Drug: Placebo plus Docetaxel

  450 mg/m2 (starting dose) IPI-504 or placebo IV (in the vein) day 1, 8 & 15 during each 21 day cycle

  75 mg/m2 in US and EU, 60 mg/m2 in South Korea and Taiwan Docetaxel (Taxotere®) will be administered by IV infusion every 3 weeks (Day 1 of each 21-day cycle)

  Other Name: Docetaxel

• Active Comparator: ARM 1: IPI 504 + Docetaxel
  Drug: IPI-504 plus Docetaxel
  Intervention: Drug: IPI 504 plus Docetaxel
• Placebo Comparator: Placebo + Docetaxel
  Placebo plus Docetaxel
  Intervention: Drug: Placebo plus Docetaxel

Inclusion Criteria:

• Patients must be ≥18 years of age
• Voluntarily signed an informed consent
• Confirmed NSCLC and Stage IIIB or IV disease.
• At least a ≥15 pack year smoking history and must have been an active smoker within 20 years of diagnosis.
• Must have archival NSCLC tissue available to provide for analysis or have a lesion that is accessible for biopsy
• Must have experienced disease progression during or after receiving at least 1 prior platinum-containing chemotherapy regimen.
• Must have received no more than 2 prior chemotherapy regimens
• Measurable disease by RECIST 1.1 criteria.
• ECOG performance status of 0 or 1 (Refer to scale in Appendix 1).
• Women of child-bearing potential (WCBP), all sexually active male patients, and partners of patients must agree to use adequate methods of birth control.

Exclusion Criteria:

• Prior docetaxel, IPI-504 or other Hsp90 inhibitor treatment
• Known hypersensitivity to drugs formulated with polysorbate-80.
• Not recovered from any toxicities related to prior treatment
• Use of a medication or food that is a clinically relevant CYP3A inhibitor or inducer
• Inadequate hematologic function
• Inadequate hepatic function
• Inadequate renal function
• Symptomatic keratitis or keratoconjunctivitis.
• Uncontrolled systemic fungal, bacterial, viral or other infection
• Patients with clinically active brain metastases
• Patients with clinically stable brain metastases (previously treated or untreated) are eligible.
• Sinus bradycardia (resting heart rate <50 bpm).
• Significant cardiac disease
• Previous or current malignancies at other sites within the last 2 years
• Prior hepatic resections or hepatic-directed therapy
• Known HIV-positive patients receiving combination antiretroviral therapy.
• Women who are pregnant or lactating.