A Phase 1 Dose Escalation Study of IPI-493

Advanced Malignancies Clinical Trial

Official title:

A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of IPI-493 Orally Administered to Patients With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00724425
• Other study ID #: IPI-493-01
• Status: Terminated
• Phase: Phase 1
• First received: July 25, 2008
• Last updated: April 14, 2015
• Start date: July 2008
• Est. completion date: July 2011

Study information

• Verified date: April 2015
• Source: Infinity Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 53
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms

Intervention

Drug:
• IPI-493
Capsules, Multiple Schedules

Locations

Country	Name	City	State
United States	Univeristy of Colorado Health Science Center	Aurora	Colorado
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	San Diego Pacific Oncology and Hematology Associates	Encinitas	California
United States	Premiere Oncology, California	Santa Monica	California
United States	Premiere Oncology, Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Infinity Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety and maximum tolerated dose (MTD) of IPI 493		ongoing	Yes
Primary	To recommend a dosing regimen (dose and schedule) for subsequent studies of IPI 493		ongoing	Yes