A Phase 1 Dose Escalation Study of IPI-493

Sponsor

Infinity Pharmaceuticals, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00724425

Collaborator

(none)

Enrollment

Locations

Duration (Months)

10.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancies	Drug: IPI-493	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Outcome Measures

Primary Outcome Measures

To determine the safety and maximum tolerated dose (MTD) of IPI 493 [ongoing]
To recommend a dosing regimen (dose and schedule) for subsequent studies of IPI 493 [ongoing]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have pathologically confirmed advanced solid tumors
Progressive disease for their advanced solid tumor
Patients must be ≥18 years of age
Performance status of 0 or 1.
Not Pregnant by blood or urine test, and be willing to use adequate methods of birth control

Exclusion Criteria:

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

Toxicities from prior therapies must have resolved to ≤ Grade 1 or baseline
Concurrent administration of the medications or foods , which are known to inhibit or induce CYP3A activity to a clinically relevant degree, is not allowed.
Concurrent treatment with any agent known to prolong the QTc interval
Known human immunodeficiency virus (HIV) positivity.
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
Inadequate hepatic function
Inadequate renal function
Sinus bradycardia
Baseline QTcF > 450 msec in males; QTcF > 470 msec in females.
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.
Patients who have received > 450 mg/m2 of any anthracycline during prior chemotherapy must have a baseline left ventricular ejection fraction (LVEF) > 40%.
Active keratitis or keratoconjunctivitis.
Presence of active infection or systemic use of antibiotics within 72 hours of treatment.
Patients with a clinically active brain metastasis
Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
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.
Women who are pregnant or lactating.
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

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology, Arizona	Scottsdale	Arizona	United States	85260
2	San Diego Pacific Oncology and Hematology Associates	Encinitas	California	United States	92024
3	Premiere Oncology, California	Santa Monica	California	United States	90404
4	Univeristy of Colorado Health Science Center	Aurora	Colorado	United States	80045
5	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Infinity Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00724425

Other Study ID Numbers:

IPI-493-01

First Posted:

Jul 29, 2008

Last Update Posted:

Apr 15, 2015

Last Verified:

Apr 1, 2015

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Apr 15, 2015