Cilengitide in Treating Patients With Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00121238
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 130
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer	Drug: cilengitide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the rate of Prostate Specific Antigen response associated with EMD121974 therapy in patients with non-metastatic androgen-independent prostate cancer.

SECONDARY OBJECTIVES:

1. To evaluate the safety of EMD121974 in patients with non-metastatic androgen-independent prostate cancer.

2. To assess the change in the slope of Prostate Specific Antigen associated with EMD121974 in patients with non-metastatic androgen-independent prostate cancer.

3. To assess response duration, time to progression and survival.

TERTIARY OBJECTIVES:

1. 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.

2. To study the genotypic/phenotypic variances in circulating tumor cells in patients with non-metastatic androgen-independent prostate cancer before and after EMD121974 treatment.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

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 Names: EMD 121974

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Median PSA Slope Difference [Baseline to 6 months]

   Median PSA slope difference was calculated between baseline and 6 months.

2. 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.

3. 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.

4. Mean Time to Progression of Prostate Cancer [Up to 5 years]

   Kaplan-Meier estimates of time to progression will be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00121238
• Other Study ID Numbers: NCI-2012-03066; 2004-045; N01CM62206; CDR0000438708
• First Posted: Jul 21, 2005
• Last Update Posted: Apr 28, 2016
• Last Verified: Feb 1, 2013

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	16 patients were registered to the protocol at 6 centers between January 2005 and May 2007.
Pre-assignment Detail	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

Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Period Title: Overall Study
STARTED	16
COMPLETED	13
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Overall Participants	13
Age, Customized (years) [Median (Full Range) ]
age in years	65.5
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	13 100%
Region of Enrollment (participants) [Number]
United States	13 100%
Prostate Specific Antigen (PSA) (ng/mL) [Median (Full Range) ]
Median (Full Range) [ng/mL]	8.4
Gleason sum (participants) [Number]
Gleason sum 6	2 15.4%
Gleason sum 7	6 46.2%
Gleason sum 8	2 15.4%
Gleason sum 9	3 23.1%
Karnofsky Performance Score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	90
Prior radiation to prostate (participants) [Number]
Definitive	5 38.5%
Adjuvant	3 23.1%
Salvage	3 23.1%
Radical Prostatectomy (participants) [Number]
Number [participants]	6 46.2%
No Local Treatment Modality (participants) [Number]
Number [participants]	2 15.4%
Median time since ADT initiation (years) [Median (Full Range) ]
Median (Full Range) [years]	4.7

Outcome Measures

1. Primary Outcome

Title	The Number of Patients With a PSA Decline of ≥50%
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Measure Participants	13
Number [participants]	0 0%

2. Secondary Outcome

Title	Median PSA Slope Difference
Description	Median PSA slope difference was calculated between baseline and 6 months.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Measure Participants	13
Median (Inter-Quartile Range) [ng/mL/month]	0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drug Treatment (Cilengitide)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	The Number of Participants With at Least One Incident of Toxicity
Description	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

Outcome Measure Data

Analysis Population Description

All treated patients, including 2 patients who were deemed ineligible for the study's endpoints to measure efficacy.

Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Measure Participants	15
Number [participants]	15 115.4%

4. Secondary Outcome

Title	Median Survival Time
Description	6 of 13 patients were alive at five years. The Median survival time was calculated for all patients.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Measure Participants	13
Median (95% Confidence Interval) [months]	34.5

5. Secondary Outcome

Title	Mean Time to Progression of Prostate Cancer
Description	Kaplan-Meier estimates of time to progression will be reported.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

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/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
Measure Participants	13
Mean (95% Confidence Interval) [months]	1.8

Adverse Events

Time Frame	During treatment with study drug for 1 year if toxicity did not halt treatment
Adverse Event Reporting Description	Toxicity was evaluated by NCI-CTCAE (ver. 3) criteria in all 15 treated patients including the 2 ineligible patients. No Grade 4 events,2 grade 3 events, 3 grade 2 events and 22 grade 1 adverse events.
Arm/Group Title	Drug Treatment (Cilengitide)
Arm/Group Description	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
All Cause Mortality
	Drug Treatment (Cilengitide)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Drug Treatment (Cilengitide)
	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)
Cardiac disorders
atrial fibrillation	2/15 (13.3%)
Other (Not Including Serious) Adverse Events
	Drug Treatment (Cilengitide)
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Increased aspartate aminotransferase (Gr1)	1/15 (6.7%)
Decreased hemoglobin (gr1)	2/15 (13.3%)
Lymphopenia (Gr.2)	1/15 (6.7%)
Eye disorders
Dry eye syndrome (Gr1)	1/15 (6.7%)
Gastrointestinal disorders
Constipation (Gr1)	1/15 (6.7%)
Diarrhea (Gr1)	1/15 (6.7%)
Nausea Gr 1	1/15 (6.7%)
Toothache (Gr.1)	1/15 (6.7%)
General disorders
Edema (Gr.1)	1/15 (6.7%)
Fatigue (Gr.1)	4/15 (26.7%)
Flushing (Gr1)	1/15 (6.7%)
Headache (Gr.1)	1/15 (6.7%)
Hyponatremia (Gr.1)	1/15 (6.7%)
Metabolism and nutrition disorders
Hyperglycemia NOS (Gr.1)	1/15 (6.7%)
Hyperglycemia (Gr.1)	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Arthritis (Gr1)	2/15 (13.3%)
Osteonecrosis (Gr.2)	1/15 (6.7%)
Nervous system disorders
Memory impairment (Gr.1)	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (Gr.2)	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Rash (desquamating) (Gr.1)	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.