Study of ATN-224 in Patients With Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Randomized, Phase II Study of Two Dose Levels of ATN-224 in Patients With Biochemically Relapsed, Early Stage Prostate Cancer Not on Hormone Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00405574
• Other study ID #: ATN-224-005
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 29, 2006
• Last updated: January 28, 2008
• Start date: November 2006
• Est. completion date: September 2008

Study information

• Verified date: January 2008
• Source: Attenuon
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized, phase II study of the safety and efficacy of two dose levels of oral ATN-224 in patients with prostate cancer with a rising serum PSA in the absence of detectable disease. Patients will be randomized (1:1) after confirmation of eligibility requirements. The primary endpoint is to determine the proportion of patients who do not have PSA progression for 24 weeks. PSA progression is defined as at least a 50% increase in PSA and >5 ng/mL from baseline or post-treatment nadir if lower than baseline, confirmed by another PSA at least 28 days later.

Description:

ATN-224 is an orally active, small molecule that has been shown in cellular and animal models to be anti-angiogenic and to have activity against prostate cancer cell lines. ATN-224 has the potential to affect the progression of prostate cancer by mechanisms that include both antiangiogenic and antitumor pathways. ATN-224 may change the time to overt metastatic disease in patients with rising PSA as the only manifestation of disease after treatment with curative intent and delay the need for hormonal therapies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: September 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Patients with histologically confirmed, localized prostate cancer who have a prostate-specific antigen (PSA) doubling time (DT) as calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (http://www.mskcc.org/mskcc/html/10088.cfm)

• Doubling time < 12 months after local therapy in patients who have not had any previous hormone therapy, or

• Doubling time < 12 months starting at least 6 months after their last dose of hormone therapy

• Patients must have a serum testosterone >150 ng/dL at the time of study entry. Patients may have received previous castrating hormonal therapy or anti-androgens, provided that the testosterone level is >150 ng/dL at the time of study entry. Prior chemotherapy is also allowed as long as the requirements for adequate organ and marrow function are met.

• No detectable disease as assessed by physical examination and bone and CT (abdomen and pelvis) scans within 4 weeks prior to the first dose of ATN-224

• A minimum of three PSA values, each at least 4 weeks apart, to calculate PSA-DT. The last PSA level prior to enrollment must be at least 2.0 ng/mL and be rising over the prior value.

• Age =18 years

• Life expectancy of greater than 6 months

• Eastern Cooperative Oncology Group (ECOG) performance status =2 (Karnofsky =50%; see Appendix A)

• Patients must have adequate organ and marrow function as defined below:

• absolute neutrophil count =1,500/uL

• platelets =100,000/uL

• hemoglobin =9 g/dL

• total bilirubin =2 X institutional upper limit of normal (ULN)

• AST(SGOT) and ALT(SGPT) =2 X ULN

• creatinine clearance (measured or calculated) =30 mL/min

• serum testosterone >150 ng/mL or return to pre-treatment values for patients who received hormone therapy

Patients are allowed to receive erythropoietin or blood transfusions before receiving their first dose of ATN-224 to bring the hemoglobin level to >9 g/dL to meet eligibility criteria.

• At least 28 days from receiving any investigational agent

• The effects of ATN-224 on sperm at the recommended therapeutic dose are unknown. For this reason men with partners of child-bearing potential must agree to use adequate contraception (hormonal and/or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation through the follow up visit 28 days after the last dose of ATN-224

• Willingness to forgo taking copper- or zinc-containing vitamins or supplements

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had radiotherapy within 3 months prior to the first dose of ATN 224

• Patients may not be receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ATN-224 or omeprazole or other long acting antacids

• History of malabsorption syndromes or other gastrointestinal disorders that may affect ATN-224 absorption, including bowel obstruction, celiac disease, sprue, cystic fibrosis

• Ineligible to receive either omeprazole (Prilosec®), lansoprazole (Prevacid®), pantoprazole (Protonix®), or ranitidine (Zantac®)

• Inability to swallow study medication capsules

• Other serious medical or psychiatric illness preventing informed consent or with the potential to interfere with assessment of safety or efficacy of ATN-224 treatment

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients known to be positive for HIV or infectious hepatitis type A, B or C

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer or any other cancer from which the patient has been disease-free for 5 years

• Patients receiving steroid therapy for concurrent illness unless they have been on a stable dose for 3 months.

• Patients receiving hormonal therapy including gonadotropin-releasing hormone agonist/antagonist, antiandrogens, diethylstilbestrol, any other estrogen-like agents, any hormonally active over-the-counter compounds such as PC-SPES or finasteride

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ATN-224
ATN-224 high dose: 300mg ATN-224 low dose: 30mg

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University	Baltimore	Maryland
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Attenuon	Prostate Cancer Clinical Trials Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the proportion of patients who have not had prostate specific antigen (PSA) progression for 24 weeks		24 weeks	No
Secondary	Establish the safety of the two dose levels of ATN-224		Ongoing	Yes
Secondary	Determine the proportion of patients with a 50% reduction from baseline of PSA confirmed by a second PSA value at least 28 days later		End of Study	No
Secondary	Determine the change in PSA doubling time (PSA-DT) from baseline		End of Study	No
Secondary	Determine the maximal % decrease in PSA after treatment		End of Study	No
Secondary	Determine the time to PSA progression (as defined by this protocol)		End of Study	No
Secondary	Determine the 24-week rate of metastases		24 weeks	No
Secondary	Determine the effect of ATN-224 treatment on levels of Cu,Zn-superoxide dismutase (SOD1) in red blood cells		End of Study	No