IPI-504-04: A Phase 2 Study to Investigate the Clinical Activity of IPI-504 in Patients With Hormone-resistant Prostate Cancer

Sponsor

Infinity Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00564928

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine:

Anti-tumor activity of IPI-504 in 2 groups of subjects with hormone resistant prostate cancer.
Group A - subjects who have not previously received chemotherapy
Group B - sujects who have received prior chemotherapy or could not tolerate chemotherapy.
Clinical response will be determined by PSA and radiological response

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Prostatic Neoplasms Cancer of the Prostate	Drug: IPI-504	Phase 2

Detailed Description

IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. Inhibition of HSP-90 leads to the proteasomal degradation of these proteins.

In patients with HRPC,there are several proteins that are important in the progression of HRPC, including AR, AKT and Her-2. All of these are client proteins of Hsp90 and in response to Hsp90 inhibition are degraded by their proteasome. Preclinical studies have shown that Hsp90 inhibition causes a dose dependent degradation of these client proteins and growth inhibition of prostate cancer in xenograft tumors.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Open-Label Study to Investigate the Pharmacodynamics and Clinical Activity of IPI-504 in Patients With Castration-Resistant Prostate Cancer Stratified by Prior Chemotherapy

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IPI-504: Group A No Prior treatment for prostate cancer with cytotoxic chemotherapy (adjuvant or neoadjuvant chemotherapy is acceptable if completed >2 years prior to study)	Drug: IPI-504 IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle
Experimental: IPI-504: Group B Must have evidence of radiographic metastatic disease Must have been treated with a docetaxel-based chemotherapy regimen for HRPC with a minimum of 2 cycles with either PSA or RECIST defined radiographic progression during or witin 60 days of completeing docetaxel based chemotheraph or be intolerant of docetaxel-based chemotherapy No more than three prior chemotherapies regimens for HRPC	Drug: IPI-504 IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle

Arm

Intervention/Treatment

Experimental: IPI-504: Group A

No Prior treatment for prostate cancer with cytotoxic chemotherapy (adjuvant or neoadjuvant chemotherapy is acceptable if completed >2 years prior to study)

Drug: IPI-504

IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle

Experimental: IPI-504: Group B

Must have evidence of radiographic metastatic disease Must have been treated with a docetaxel-based chemotherapy regimen for HRPC with a minimum of 2 cycles with either PSA or RECIST defined radiographic progression during or witin 60 days of completeing docetaxel based chemotheraph or be intolerant of docetaxel-based chemotherapy No more than three prior chemotherapies regimens for HRPC

Drug: IPI-504

IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle

Outcome Measures

Primary Outcome Measures

Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate [12 Weeks]

Secondary Outcome Measures

Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer [12 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Adenocarcinoma of the prostate
Resolution of acute toxic side effects of prior chemotherapy
Castration resistant disease despite ongoing chemical or surgical castration
ECOG 0-1
PSA greater than or equal to 2
Group A -
No Prior treatment for prostate cancer with cytotoxic chemotherapy (neoadjuvant, adjuvant treatment permitted if more than 2 years out)
Group B
Radiographic evidence of metastatic disease
Prior tx with docetaxel-minimum of 2 cycles with progression by RECIST or PSA or intolerant of tx
Maximum of 3 prior chemotherapies

Exclusion Criteria:

Small cell carcinoma of the prostate
Treatment within 2 weeks with approved, investigational, or small molecule
Treatment within 4 weeks with biologic or external beam radiation
ANC <1,500 cells m3; Platelets <100,000 mm3; Hemoglobin <9.0g/dL
AST/ALT >2.5 ULN
Serum creatinine >3.0mg/dL
Active keratitis or keratoconjunctivitis
Previous treatment with 17-AAG, DMAG; or any other HSP-90 inhibitor
Baseline Qtc >450 mses

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Bernardino Urological Associates	San Bernardino	California	United States	92404
2	Stanford University Medical Center	Stanford	California	United States	94305
3	University of Colorado at Denver	Denver	Colorado	United States	80045
4	MCG Cancer Center	Augusta	Georgia	United States	30912
5	University of Chicago Hospitals	Chicago	Illinois	United States	60637
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
8	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
9	Wayne State University	Detroit	Michigan	United States	48201
10	Parkland Hospital	Dallas	Texas	United States	75390