Study of ATN-224 in Patients With Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ATN-224
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring prostate, PSA, antiangiogenic, copper, ATN-224
Eligibility Criteria
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
Sites / Locations
- University of California San Francisco
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
- Memorial Sloan Kettering Cancer Center
- Oregon Health and Science University
- University of Texas MD Anderson Cancer Center
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
High Dose
Low Dose
Arm Description
ATN-224 dose 300mg
ATN-224 dose: 30mg
Outcomes
Primary Outcome Measures
Determine the proportion of patients who have not had prostate specific antigen (PSA) progression for 24 weeks
Secondary Outcome Measures
Establish the safety of the two dose levels of ATN-224
Determine the proportion of patients with a 50% reduction from baseline of PSA confirmed by a second PSA value at least 28 days later
Determine the change in PSA doubling time (PSA-DT) from baseline
Determine the maximal % decrease in PSA after treatment
Determine the time to PSA progression (as defined by this protocol)
Determine the 24-week rate of metastases
Determine the effect of ATN-224 treatment on levels of Cu,Zn-superoxide dismutase (SOD1) in red blood cells
Full Information
NCT ID
NCT00405574
First Posted
November 29, 2006
Last Updated
January 28, 2008
Sponsor
Attenuon
Collaborators
Prostate Cancer Clinical Trials Consortium
1. Study Identification
Unique Protocol Identification Number
NCT00405574
Brief Title
Study of ATN-224 in Patients With Prostate Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2008
Overall Recruitment Status
Unknown status
Study Start Date
November 2006 (undefined)
Primary Completion Date
June 2008 (Anticipated)
Study Completion Date
September 2008 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Attenuon
Collaborators
Prostate Cancer Clinical Trials Consortium
4. Oversight
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
prostate, PSA, antiangiogenic, copper, ATN-224
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High Dose
Arm Type
Experimental
Arm Description
ATN-224 dose 300mg
Arm Title
Low Dose
Arm Type
Experimental
Arm Description
ATN-224 dose: 30mg
Intervention Type
Drug
Intervention Name(s)
ATN-224
Intervention Description
ATN-224 high dose: 300mg ATN-224 low dose: 30mg
Primary Outcome Measure Information:
Title
Determine the proportion of patients who have not had prostate specific antigen (PSA) progression for 24 weeks
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Establish the safety of the two dose levels of ATN-224
Time Frame
Ongoing
Title
Determine the proportion of patients with a 50% reduction from baseline of PSA confirmed by a second PSA value at least 28 days later
Time Frame
End of Study
Title
Determine the change in PSA doubling time (PSA-DT) from baseline
Time Frame
End of Study
Title
Determine the maximal % decrease in PSA after treatment
Time Frame
End of Study
Title
Determine the time to PSA progression (as defined by this protocol)
Time Frame
End of Study
Title
Determine the 24-week rate of metastases
Time Frame
24 weeks
Title
Determine the effect of ATN-224 treatment on levels of Cu,Zn-superoxide dismutase (SOD1) in red blood cells
Time Frame
End of Study
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilad Gordon, MD
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
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Study of ATN-224 in Patients With Prostate Cancer
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