A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

A Gynecologic Oncology Group study

Michael A. Gold, William E. Brady, Heather A. Lankes, Peter G. Rose, Joseph L. Kelley, Koenraad De Geest, Marta A. Crispens, Kimberly E. Resnick, Stephen B. Howell

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC). Patients and methods: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. Results: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342). Conclusion: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

Original languageEnglish (US)
Pages (from-to)635-639
Number of pages5
JournalGynecologic Oncology
Volume125
Issue number3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Fallopian Tubes
Urokinase-Type Plasminogen Activator
Carcinoma
Disease-Free Survival
Therapeutics
acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide
Platinum
Disease Progression
Immunohistochemistry
Hemorrhage
Survival

Keywords

  • GOG
  • Ovarian cancer
  • Primary peritoneal carcinoma
  • Urokinase-derived peptide

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma : A Gynecologic Oncology Group study. / Gold, Michael A.; Brady, William E.; Lankes, Heather A.; Rose, Peter G.; Kelley, Joseph L.; De Geest, Koenraad; Crispens, Marta A.; Resnick, Kimberly E.; Howell, Stephen B.

In: Gynecologic Oncology, Vol. 125, No. 3, 06.2012, p. 635-639.

Research output: Contribution to journalArticle

Gold, Michael A. ; Brady, William E. ; Lankes, Heather A. ; Rose, Peter G. ; Kelley, Joseph L. ; De Geest, Koenraad ; Crispens, Marta A. ; Resnick, Kimberly E. ; Howell, Stephen B. / A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma : A Gynecologic Oncology Group study. In: Gynecologic Oncology. 2012 ; Vol. 125, No. 3. pp. 635-639.
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abstract = "Purpose: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC). Patients and methods: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. Results: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5{\%}) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5{\%}). Archival specimens were available for 27 patients, and 5 (18.5{\%}) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342). Conclusion: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.",
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T2 - A Gynecologic Oncology Group study

AU - Gold, Michael A.

AU - Brady, William E.

AU - Lankes, Heather A.

AU - Rose, Peter G.

AU - Kelley, Joseph L.

AU - De Geest, Koenraad

AU - Crispens, Marta A.

AU - Resnick, Kimberly E.

AU - Howell, Stephen B.

PY - 2012/6

Y1 - 2012/6

N2 - Purpose: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC). Patients and methods: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. Results: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342). Conclusion: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

AB - Purpose: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC). Patients and methods: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. Results: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342). Conclusion: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

KW - GOG

KW - Ovarian cancer

KW - Primary peritoneal carcinoma

KW - Urokinase-derived peptide

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