Cilengitide in Treating Patients With Prostate Cancer

Recurrent Prostate Cancer Clinical Trial

Official title:

Phase II Evaluation of EMD 121974 (NSC 707544, Cilengitide) in Patients With Non-Metastatic Androgen Independent Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00121238
• Other study ID #: NCI-2012-03066
• Secondary ID: 2004-045N01CM622
• Status: Completed
• Phase: Phase 2
• First received: July 19, 2005
• Last updated: January 30, 2013
• Start date: January 2005

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Recurrent Prostate Cancer
• Stage I Prostate Cancer
• Stage IIA Prostate Cancer
• Stage IIB Prostate Cancer
• Stage III Prostate Cancer

Intervention

Drug:
• cilengitide
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Michigan University Hospital	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA response, defined as a drop in PSA of at least 50% from the final pre-treatment value	Efficacy will be reported as rates plus confidence intervals.	Up to 5 years	No
Secondary	Change in PSA slope	Mean change in PSA slope will be reported, along with the percentage PSA slope decreased after treatment.	Baseline to 6 months	No
Secondary	Incidence of toxicities	The rate of toxicities, overall and by grade, will also be reported.	Up to 5 years	Yes
Secondary	Survival time	Kaplan-Meier estimates of survival time and time to progression will be reported, along with descriptive statistics on the duration of response.	Up to 5 years	No
Secondary	Time to progression	Kaplan-Meier estimates of survival time and time to progression will be reported, along with descriptive statistics on the duration of response.	Up to 5 years	No
Secondary	Duration of response	Kaplan-Meier estimates of survival time and time to progression will be reported, along with descriptive statistics on the duration of response.	Up to 5 years	No