A Study Evaluating the Safety and Antitumor Activity of IPI-504, in Patients With Metastatic Melanoma

Metastatic Melanoma Clinical Trial

Official title:

A Phase 2, Open-Label, Single-Arm, Multicenter Study Evaluating the Safety and Antitumor Activity of IPI-504, A Novel Small Molecule Inhibitor of Heat Shock Protein 90 (HSP90), in Patients With Metastatic Melanoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00627419
• Other study ID #: MI-CP159
• Status: Terminated
• Phase: Phase 2
• First received: February 21, 2008
• Last updated: December 6, 2012
• Start date: February 2008
• Est. completion date: October 2009

Study information

• Verified date: December 2012
• 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

To evaluate the antitumor activity of IPI-504 in patients with metastatic melanoma.

Description:

To evaluate the antitumor activity of IPI-504 in patients with metastatic melanoma and to assessment of antitumor activity is the 6-month progression-free rate.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed, unresectable, Stage IV or recurrent melanoma, including mucosal melanoma (based on American Joint Committee on Cancer [AJCC] staging [Balch, 2001], see Appendix A).

• Prior therapy with chemotherapy and/or immunotherapy for melanoma is allowed provided that therapy ended prior to study entry and all treatment-related toxicities have resolved to NCI CTCAE Grade = 1 or patient's baseline;

• Measurable disease (based on RECIST [Therasse, 2000]) defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as = 20 mm with conventional techniques or as = 10 mm with spiral CT scan;

• Have melanoma that can be biopsied once prior to treatment (all patients), and a second time during treatment with IPI504 (stage 2 patients);

• Willingness for tumor biopsy at screening (all patients) and once during treatment (stage 2 patients only);

• Males and females of at least 18 years of age at the time of study entry;

• Female patients must be of non child-bearing potential (defined as being >1 year post-menopausal) or using effective contraception, eg, use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, or total abstinence, from the time the informed consent is signed through 30 days after the last dose of IPI-504. Male patients must be surgically sterile or use a double-barrier method of contraception (condom with spermicide) from the time of the initiation of IPI-504 through 30 days after the last dose of IPI-504;

• Eastern Cooperative Oncology Group performance status of 0 to 2;

• Life expectancy of at least 16 weeks;

• White blood cell (WBC) count = 3,000/mm3, absolute neutrophil count (ANC) = 1,500/mm3, platelet count = 100,000/mm3; Prothrombin time or international normalized ratio within normal range (unless a patient is receiving anticoagulation therapy), or PTT within normal range;

• Serum creatinine = 1.5 × ULN and creatinine clearance = 50 mL/min (by Cockroft-Gault method);

• Total bilirubin = 1.5 × ULN [unless due to Gilbert's syndrome (unconjugated hyperbilirubinemia) in which case the total bilirubin should be = 3.5 mg/dL], AST and ALT = 2.5 × ULN, hepatic alkaline phosphatase = 2.5× ULN;

• LDH = 1.5 × ULN;

• Patients who have had prior radiation therapy are eligible provided that therapy was palliative in nature, not in the area where the tumor will be biopsied, at least one measurable lesion outside the radiation field, and all radiation-related toxicities have resolved to NCI CTCAE Grade = 1 or patient's baseline;

• Patients who had recovered from prior major surgery are eligible if all surgical wounds have healed;

• Written informed consent and HIPAA authorization obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

• Received an investigational agent or therapy with any other kinase inhibitor within 2 weeks prior to study entry or any other antitumor therapy, such as cytostatic and/or cytotoxic drugs, hormonal therapy, radiation therapy, immunotherapy, or any biological response modifiers within 4 weeks prior to study entry;

• Previous treatment with 17-AAG, 17-dimethylaminoethylamino-17-demethoxygel-danamycin (17-DMAG), or other known Hsp90 inhibitor;

• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer;

• Current or planned participation (from the day of study entry through 30 days after the last dose of IPI-504) in a research protocol in which an investigational agent or therapy may be administered;

• Initiation or discontinuation of concurrent medication that alters CYP3A activity (see Appendix C) within 2 weeks prior to treatment with IPI-504. Patients who are on a stable dose of drugs known to alter CYP3A activity for > 2 weeks are eligible to enroll;

• Presence of active infection or systemic use of antimicrobials within 72 hours prior to treatment with IPI-504;

• Known brain metastases or primary brain tumors. Patients with = 2 lesions are eligible provided:

• Treated with surgery or stereotactic radiosurgery

• The lesions are < 3 cm in size and have been stable for 2 months (by CT/MRI)

• The patient has been off steroids for at least 1 week prior to dosing and:

• The patient is allowed to have had whole brain radiation if performed in conjunction with surgery/stereotactic radiotherapy and the last dose of radiation occurred at least 2 months prior to dosing with IPI504.

• Significant comorbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study (eg, cardiac disease such as acute coronary syndrome or unstable angina within 6 months, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident, or other conditions);

• History of prior malignancies within the past 5 years other than non-melanomatous skin cancers that have been controlled, carcinoma in situ of the cervix, T1a or b prostate cancer noted incidentally during a transurethral resection of prostate (TURP) with prostate-specific antigen values within normal limits since TURP, or superficial bladder cancer;

• Women who are pregnant or lactating;

• Sinus bradycardia (resting heart rate < 50 beats/min) 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;

• Screening QTc > 450 msec in males; QTc > 470 msec in females, or previous history of QTc prolongation while taking other medications; or

• Active or recent history (within 3 months) of keratitis or keratoconjunctivitis, confirmed by ophthalmology or optometry exam.

Study Design

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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• IPI-504
Dose as a 30 to 60 minute IV infusion as part of a 21-day treatment cycle until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for patient withdrawal. IPI-504 will be administered twice weekly on Study Days 1, 4, 8, and 11 of each 21-day cycle.

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	Univ. of TX, MD Anderson Cancer Center	Houston	Texas
United States	Indiana Univ. Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Univ. of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Mayo Comprehensive Cancer Center	Rochester	Minnesota
United States	Sharp Memorial Hospital	San Diego	California
United States	Washington School of Medicine	St. Louis	Missouri
United States	Arizona Cancer Center	Tuscon	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	Evaluating the antitumor activity of IPI-504 in patients with metastatic melanoma. The primary assessment of antitumor activity is the 6-month progression-free rate.		from the first administration of IPI-504 through 30 days after the last dose of IPI-504	Yes
Secondary	Evaluating other antitumor activities, safety, and PK parameters of IPI-504 in this patient population.		from the first administration of IPI-504 through 30 days after the last dose of IPI-504 (confirm)	Yes