IPI-504 in NSCLC Patients With ALK Translocations
Condition: Lung Cancer; Stage IIIb Lung Cancer; Stage IV Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: IPI-504
Intervention description: Given intravenously twice weekly for 2 weeks followed by 10 day off treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC; IPI-504; ALK translocation; Hsp90 inhibitor

Summary:

      IPI-504 blocks a protein that is in cancer cells and is also in normal cells. This protein is
      called Heat Shock Protein-90 (Hsp90). Hsp90 helps protect certain other proteins from being
      destroyed by cells. These proteins can mutate to give off signals that allow cancer cells to
      keep growing. By blocking the function of Hsp90, we hope that the cancer cell will block the
      mutated protein and cause the cancer cells to die. This drug have been used in other research
      studies and in the laboratory and information from those other research studies suggests that
      thsi drug may help to treat lung cancer with ALK mutations. In this research study, we are
      looking to see what effects IPI-504 has in patients with lung cancer who have an ALK
      mutation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically confirmed diagnosis of Stage IIIb (with malignant
             pleural or pericardial effusion), Stage IV, or recurrent NSCLC.

          -  Patients must have demonstrated ALK mutation

          -  There is no requirement for a minimum or maximum number of prior therapies, however,
             patients must have refused, be intolerant to or already received at least on standard
             systemic therapy for lung cancer

          -  Measureable disease by RECIST criteria. If a patient has received radiation therapy
             then measurable disease must be outside the radiation field.

          -  18 years of age or older

          -  Life expectancy of at least 3 months

          -  ECOG performance status of 0-2

          -  Baseline studies for determining eligibility, except for ALK mutation status, must be
             completed within 30 days of first study dose.

          -  CT scan must be completed within 28 days prior to first study dose

          -  Women of child-bearing potential (WBCP) defined as a sexually mature woman who has not
             undergone a hysterectomy or who has not been naturally post-menopausal for at least 24
             consecutive months must have a negative serum or urine pregnancy test within 2 weeks
             of first study dose

          -  All WCBP and all sexually active male patients must agree to use adequate methods of
             birth control throughout the study

        Exclusion Criteria:

          -  Treatment for NSCLC with any approved or investigational product within 2 weeks of
             Cycle 1, Dose 1 for any small molecule therapy; within 4 weeks of Cycle 1, Dose 1 for
             any biologic or any conventional chemotherapy.

          -  Concurrent radiation therapy is not permitted

          -  Use of a medication or food that is clinically relevant CYP3A inhibitor or inducer
             within 2 weeks prior to Cycle 1, Dose 1

          -  Laboratory values as outlined in the protocol

          -  Baseline QT corrected using Fridericia's correction method (QTcf) > 470ms. Patients
             with left bundle branch block are eligible regardless of QTcf, as long as serum
             troponin is normal or undetectable

          -  Presence of active infection or systemic use of antibiotics within 72 hours of
             treatment

          -  Significant co-morbid condition or disease which in the judgment of the investigator
             would place the patient at undue risk or interfere with the study

          -  Women who are pregnant or lactating

          -  Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor

          -  Sinus bradycardia secondary to intrinsic conduction system disease. Patients with
             sinus bradycardia secondary to pharmacologic treatment may enroll if withdrawal of the
             treatment results in normalization of the resting heart rate to within normal limits

          -  Active keratitis or keratoconjunctivitis

          -  Alkaline phosphatase > 1.5 x ULN. Patients with bone metastases and an alkaline
             phosphatase level > 1/5 x ULN and less than or equal to 3 x ULN are eligible if they
             meet the criteria outlined in the protocol

          -  Prothrombin time (PT) and partial thromboplastin time (PTT) > 1.5 x ULN unless the
             patient is receiving warfarin. If the patient is receiving warfarin, the international
             normalized ratio must be within therapeutic range

          -  Patients with clinically active brain metastasis or an uncontrolled seizure disorder,
             ongoing spinal cord compression, or carcinomatous meningitis. Patients with clinically
             stable brain metastasis are eligible.

          -  Patients with prior hepatic resection or hepatic-directed therapy