A Phase 1 Dose Escalation Study of IPI-493

This study has been terminated.
(Drug exposure of retaspimycin HCl was superior to IPI-493, Infinity will focus exclusively on retaspimycin)
Sponsor:
Information provided by:
Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00724425
First received: July 25, 2008
Last updated: June 10, 2011
Last verified: June 2011
  Purpose

IPI-493 is a potent inhibitor of heat shock protein 90 (Hsp90) and is orally bioavailable via a novel formulation.


Condition Intervention Phase
Advanced Malignancies
Drug: IPI-493
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of IPI-493 Orally Administered to Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Infinity Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To determine the safety and maximum tolerated dose (MTD) of IPI 493 [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]
  • To recommend a dosing regimen (dose and schedule) for subsequent studies of IPI 493 [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]

Enrollment: 53
Study Start Date: July 2008
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: IPI-493
    Capsules, Multiple Schedules
Detailed Description:

Hsp90 controls the proper folding, function, and stability of various "client" proteins within cells. Many of the clients of Hsp90 (such as Akt, Bcr-Abl, EGFR, Flt-3, c-Kit and PDGFR α) are oncoproteins or important cell-signaling proteins, and therefore are critical for tumor cell growth and survival. Inhibition of Hsp90 results in degradation of these proteins, which abrogates growth and survival signaling and leads to tumor cell death.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 control

Exclusion Criteria:

  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 by pacemaker.
  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 treatment.
  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 months.
  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 excluded:

    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00724425

Locations
United States, Arizona
Premiere Oncology, Arizona
Scottsdale, Arizona, United States, 85260
United States, California
San Diego Pacific Oncology and Hematology Associates
Encinitas, California, United States, 92024
Premiere Oncology, California
Santa Monica, California, United States, 90404
United States, Colorado
Univeristy of Colorado Health Science Center
Aurora, Colorado, United States, 80045
United States, Texas
Mary Crowley Cancer Research Center
Dallas, Texas, United States, 75201
Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
Investigators
Study Director: Robert Ross, MD Infinity Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Travis Quigley / Clinical Trial Manager, Infinity Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00724425     History of Changes
Other Study ID Numbers: IPI-493-01
Study First Received: July 25, 2008
Last Updated: June 10, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 01, 2014