Recurrent Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage I Prostate Cancer
Conditions
Brief summary
This phase II trial is studying how well cilengitide works in treating patients with prostate cancer. Cilengitide may stop the growth of prostate cancer by blocking blood flow to the tumor
Detailed description
PRIMARY OBJECTIVES: I. To assess the rate of Prostate Specific Antigen response associated with EMD121974 therapy in patients with non-metastatic androgen-independent prostate cancer. SECONDARY OBJECTIVES: I. To evaluate the safety of EMD121974 in patients with non-metastatic androgen-independent prostate cancer. II. To assess the change in the slope of Prostate Specific Antigen associated with EMD121974 in patients with non-metastatic androgen-independent prostate cancer. III. To assess response duration, time to progression and survival. TERTIARY OBJECTIVES: I. To determine the effects of integrin αvβ3 and αvβ5 inhibition on total circulating tumor and endothelial cells isolated from peripheral blood and bone marrow aspirates from patients with non-metastatic androgen-independent prostate cancer. II. To study the genotypic/phenotypic variances in circulating tumor cells in patients with non-metastatic androgen-independent prostate cancer before and after EMD121974 treatment. III. To develop a genetic profile by cDNA microarray analysis of circulating tumor cells isolated from patients with non-metastatic androgen-independent prostate cancer before and after integrin αvβ3 and αvβ5 inhibition. OUTLINE: This is an open-label, multicenter study. Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. After 3 courses, patients undergo evaluation. Patients achieving a complete prostate-specific antigen (PSA) response (i.e., PSA \< 0.2 ng/mL) receive 2-3 additional courses of therapy. Patients with partial PSA response or stable disease continue treatment indefinitely in the absence of disease progression or unacceptable toxicity. Patients demonstrating disease progression by CT scan, MRI, or bone scan are removed from the study.
Interventions
DRUGcilengitide
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A histologic or cytologic diagnosis of prostate cancer * No evidence of metastatic disease, or local progression * PSA-only progression despite androgen deprivation therapy and antiandrogen withdrawal (28 days for flutamide and 42 days for bicalutamide or nilutamide); PSA progression is defined as 3 consecutive rising levels, with an interval of \> 1 week between each determination; the last determination must have a minimum value of \>= 2 ng/ml and be determined within two weeks prior to registration * If the third confirmatory value is less than the previous value, the patient will still be eligible if a repeat value (No. 4) is found to be greater than the second value * Patients must continue on LHRH agonists; they also may continue on any stable doses (considered stable, if on current medicine dosing for one month or longer) of megace or corticosteroids; they must be off all other therapies intended to treat the cancer for 4 weeks * ECOG performance status of 0-2 * No prior EMD 121974 therapy is allowed * No investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy * Testosterone \< 50 ng/dl; patients must continue primary androgen deprivation with an LHRH agonist, if they have not undergone orchiectomy * Four weeks must have elapsed since major surgery * Life expectancy of greater than 6 months * Patients must have normal organ and marrow function as defined below obtained within 14 days prior to registration: * ANC \>= 1,500/µl * Platelet count \>= 100,000/ µl * Creatinine =\< 1.5 x upper limits of normal * Bilirubin within normal limits * SGOT (AST) =\< 2.5 x upper limits of normal * SGPT (ALT) =\< 2.5 x upper limits of normal * PSA \>= 2 ng/ml * The effects of EMD 121974 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because antiangiogenic agents are known to be teratogenic, men must agree to use adequate contraception prior to study entry and for the duration of study participation * Ability to understand and the willingness to sign a written informed consent that is approved by the Institutional Human Investigation Committee
Exclusion criteria
* Patients may continue on a daily Multi-Vitamin, but all other herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort, etc.) must be discontinued before registration * Patients on stable doses of bisphosphonates which have been started no less than 6 weeks prior to protocol therapy, that show subsequent PSA progression, may continue on this medication, however patients are not allowed to initiate bisphosphonate therapy immediately prior or during the study * 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 with a currently active second malignancy, other than non-melanoma skin cancers or superficial bladder cancer, are not eligible; patients are not considered to have a currently active malignancy if they have completed therapy and are now considered without evidence of disease for 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With a PSA Decline of ≥50% | Up to 5 years | To assess the rate of Prostate Specific Antigen response associated with EMD121974 therapy in patients with non-metastatic androgen-independent prostate cancer. This measure defined as a drop in PSA of at least 50% from the final pre-treatment value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median PSA Slope Difference | Baseline to 6 months | Median PSA slope difference was calculated between baseline and 6 months. |
| The Number of Participants With at Least One Incident of Toxicity | Up to 5 years | Toxicity was evaluated by NCI-CTCAE (ver. 3) criteria in all 15 treated patients (16 patients were enrolled however one progressed prior to treatment) including the two ineligible patients. |
| Median Survival Time | Up to 5 years | 6 of 13 patients were alive at five years. The Median survival time was calculated for all patients. |
| Mean Time to Progression of Prostate Cancer | Up to 5 years | Kaplan-Meier estimates of time to progression will be reported. |
Countries
United States
Participant flow
Recruitment details
16 patients were registered to the protocol at 6 centers between January 2005 and May 2007.
Pre-assignment details
1 patient progressed clinically before any treatment and was not included in toxicity or efficacy endpoint analysis. Two patients who received drug were deemed ineligible because of PSA rise requirement and withdrawn for analysis for efficacy but their data was entered into toxicity analysis
Participants by arm
| Arm | Count |
|---|---|
| Drug Treatment (Cilengitide) Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. After 3 courses, patients undergo evaluation. Patients achieving a complete prostate-specific antigen (PSA) response (i.e., PSA \< 0.2 ng/mL) receive 2-3 additional courses of therapy. Patients with partial PSA response or stable disease continue treatment indefinitely in the absence of disease progression or unacceptable toxicity. Patients demonstrating disease progression by CT scan, MRI, or bone scan are removed from the study.
cilengitide : Given IV
Experimental drug treatment : Correlative studies | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | disease progression before intervention | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Drug Treatment (Cilengitide) |
|---|---|
| Age, Customized age in years | 65.5 years |
| Gleason sum Gleason sum 6 | 2 participants |
| Gleason sum Gleason sum 7 | 6 participants |
| Gleason sum Gleason sum 8 | 2 participants |
| Gleason sum Gleason sum 9 | 3 participants |
| Karnofsky Performance Score | 90 units on a scale |
| Median time since ADT initiation | 4.7 years |
| No Local Treatment Modality | 2 participants |
| Prior radiation to prostate Adjuvant | 3 participants |
| Prior radiation to prostate Definitive | 5 participants |
| Prior radiation to prostate Salvage | 3 participants |
| Prostate Specific Antigen (PSA) | 8.4 ng/mL |
| Radical Prostatectomy | 6 participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 2 / 15 |
Outcome results
Primary
The Number of Patients With a PSA Decline of ≥50%
To assess the rate of Prostate Specific Antigen response associated with EMD121974 therapy in patients with non-metastatic androgen-independent prostate cancer. This measure defined as a drop in PSA of at least 50% from the final pre-treatment value.
Time frame: Up to 5 years
Population: Per protocol: of the 16 patients registered for this arm, 13 were analyzed. 1 patient lost eligibility due to disease progression, 2 others were censored from efficacy analysis because it was determined they were ineligible based on PSA requirements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug Treatment (Cilengitide) | The Number of Patients With a PSA Decline of ≥50% | 0 participants |
Secondary
Mean Time to Progression of Prostate Cancer
Kaplan-Meier estimates of time to progression will be reported.
Time frame: Up to 5 years
Population: Patients were eligible if they had a histologic or cytologic diagnosis of prostate cancer with no evidence of metastatic disease or local progression on radiologic imaging and had 3 consecutive rising levels of prostate specific antigen (psa). Eligible patients who were treated on this trial were analyzed for survival
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Drug Treatment (Cilengitide) | Mean Time to Progression of Prostate Cancer | 1.8 months |
Secondary
Median PSA Slope Difference
Median PSA slope difference was calculated between baseline and 6 months.
Time frame: Baseline to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Drug Treatment (Cilengitide) | Median PSA Slope Difference | 0.9 ng/mL/month |
p-value: 0.27Wilcoxon (Mann-Whitney)
Secondary
Median Survival Time
6 of 13 patients were alive at five years. The Median survival time was calculated for all patients.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Drug Treatment (Cilengitide) | Median Survival Time | 34.5 months |
Secondary
The Number of Participants With at Least One Incident of Toxicity
Toxicity was evaluated by NCI-CTCAE (ver. 3) criteria in all 15 treated patients (16 patients were enrolled however one progressed prior to treatment) including the two ineligible patients.
Time frame: Up to 5 years
Population: All treated patients, including 2 patients who were deemed ineligible for the study's endpoints to measure efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug Treatment (Cilengitide) | The Number of Participants With at Least One Incident of Toxicity | 15 participants |