A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of IPI-493 Orally Administered to Patients With Advanced Malignancies
1. Patients must have pathologically confirmed advanced solid tumors
2. Progressive disease for their advanced solid tumor
3. Patients must be ≥18 years of age
4. Performance status of 0 or 1.
5. Not Pregnant by blood or urine test, and be willing to use adequate methods of birth
1. Treatment with the following therapies within the specified time period:
- Any chemotherapy (other than nitrosoureas or mitomycin C), radiation therapy
(other than whole brain irradiation [WBI]), surgery, hormonal therapy, or
investigational therapy within 4 weeks of the start of IPI 493 administration
- Any tyrosine kinase inhibitor (e.g., erlotinib, imatinib) within 2 weeks
- Whole brain irradiation therapy within 3 months
- Stereotactic cranial radiosurgery (SRS) within 4 weeks
- Nitrosoureas or mitomycin C within 6 weeks
- Any known Hsp90 inhibitor
2. Toxicities from prior therapies must have resolved to ≤ Grade 1 or baseline
3. Concurrent administration of the medications or foods , which are known to inhibit or
induce CYP3A activity to a clinically relevant degree, is not allowed.
4. Concurrent treatment with any agent known to prolong the QTc interval
5. Known human immunodeficiency virus (HIV) positivity.
6. Inadequate hematologic function defined by absolute neutrophil count (ANC) < 1,500
cells/mm3, a platelet count < 100,000/mm3, and a hemoglobin < 9.0 g/dL
7. Inadequate hepatic function
8. Inadequate renal function
9. Sinus bradycardia
10. Baseline QTcF > 450 msec in males; QTcF > 470 msec in females.
11. Presence of left bundle branch block (LBBB), right bundle branch block (RBBB) if
accompanied by left anterior hemiblock, bifascicular block or 3rd degree heart block.
This does not include patients with a history of these events with adequate control
12. Patients who have received > 450 mg/m2 of any anthracycline during prior chemotherapy
must have a baseline left ventricular ejection fraction (LVEF) > 40%.
13. Active keratitis or keratoconjunctivitis.
14. Presence of active infection or systemic use of antibiotics within 72 hours of
15. Patients with a clinically active brain metastasis
16. Patients with a history of stroke, unstable angina, myocardial infarction, or
ventricular arrhythmia requiring medication or mechanical control within the last 6
17. 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. Examples include,
but are not limited to cirrhotic liver disease, sepsis, and other conditions.
18. Women who are pregnant or lactating.
19. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep
vein thrombosis) requiring anticoagulation and meet any of the following criteria are
- Have been on a stable dose of anticoagulation for <1 month
- Have had a Grade 2, 3 or 4 hemorrhage in the past month
- Are experiencing continued symptoms from their venous thromboembolic event
- Patients who have had a venous thromboembolic event but do not meet any of
the above three criteria are eligible for participation.