Cilengitide in Treating Patients With Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00121238
First received: July 19, 2005
Last updated: March 28, 2016
Last verified: February 2013
  Purpose
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

Condition Intervention Phase
Recurrent Prostate Cancer
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Drug: cilengitide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of EMD 121974 (NSC 707544, Cilengitide) in Patients With Non-Metastatic Androgen Independent Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • The Number of Patients With a PSA Decline of ≥50% [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • Median PSA Slope Difference [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    Median PSA slope difference was calculated between baseline and 6 months.

  • The Number of Participants With at Least One Incident of Toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of time to progression will be reported.


Enrollment: 16
Study Start Date: January 2005
Study Completion Date: November 2015
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental 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.
Drug: cilengitide
Given IV
Other Name: EMD 121974

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121238

Locations
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Maha Hussain University of Michigan University Hospital
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00121238     History of Changes
Other Study ID Numbers: NCI-2012-03066  2004-045  N01CM62206  CDR0000438708 
Study First Received: July 19, 2005
Results First Received: July 29, 2015
Last Updated: March 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on May 30, 2016