Phase II study of cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium.

Abstract

BACKGROUND:

Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of cilengitide, a selective antagonist of α(v)β(3) and α(v)β(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA.

METHODS:

Patients were observed for 4 weeks with PSA monitoring, and then treated with 2,000 mg IV of cilengitide twice weekly until toxicity/progression. PSA, circulating tumor cells (CTCs) and circulating endothelial cells (CECs) were monitored each cycle with imaging performed every three cycles. Primary end point was PSA decline by ≥ 50%. Secondary endpoints were safety, PSA slope, time to progression (TTP), overall survival (OS), CTCs, CECs and gene expression.

RESULTS:

16 pts were enrolled; 13 were eligible with median age 65.5 years, baseline PSA 8.4 ng/mL and median Gleason sum 7. Median of three cycles was administered. Treatment was well tolerated with two grade three toxicities and no grade four toxicities. There were no PSA responses; 11 patients progressed by PSA after three cycles. Median TTP was 1.8 months and median OS has not been reached. Median pre- and on-treatment PSA slopes were 1.1 and 1.8 ng/mL/month. Baseline CTCs were detected in 1/9 patients. CTC increased (0 to 1; 2 pts), remained at 0 (2 pts) or decreased (23 to 0; 1 patient) at progression. Baseline median CEC was 26 (0-61) and at progression, 47 (15-148). Low cell counts precluded gene expression studies.

CONCLUSIONS:

Cilengitide was well tolerated but had no detectable clinical activity. CTCs are of questionable utility in non-metastatic prostate cancer.

• Authors: Ajjai Alva, Susan Slovin, Stephanie Daignault, Michael Carducci, Robert Dipaola, Ken Pienta, David Agus, Kathleen Cooney, Alice Chen, David C Smith, Maha Hussain
• Journal: Investigational new drugs (Invest New Drugs) Vol. 30 Issue 2 Pg. 749-57 (Apr 2012) ISSN: 1573-0646 [Electronic] United States
• PMID: 21049281 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Antineoplastic Agents
• Integrin alphaVbeta3
• Receptors, Vitronectin
• Snake Venoms
• integrin alphaVbeta5
• Cilengitide
• Prostate-Specific Antigen

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Disease Progression
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Endothelial Cells (drug effects, metabolism)
• Humans
• Infusions, Intravenous
• Integrin alphaVbeta3 (antagonists & inhibitors, metabolism)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Grading
• Neoplastic Cells, Circulating (drug effects, pathology)
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (drug therapy, metabolism, mortality, pathology)
• Receptors, Vitronectin (antagonists & inhibitors, metabolism)
• Snake Venoms (administration & dosage, adverse effects, therapeutic use)
• Time Factors
• Treatment Failure
• United States