A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

Sharad A. Ghamande; Michael H. Silverman; Warner Huh; Kian Behbakht; Greg Ball; Luceli Cuasay; Sidse Ørnbjerg Würtz; Nils Brunner; Michael A. Gold

doi:10.1016/j.ygyno.2008.06.028

A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

Sharad A. Ghamande, Michael H. Silverman, Warner Huh, Kian Behbakht, Greg Ball, Luceli Cuasay, Sidse Ørnbjerg Würtz, Nils Brunner, Michael A. Gold

35 Citations (Scopus)

Abstract

OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian cancer. METHODS: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose A6 (150 mg), or high-dose A6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of A6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. RESULTS: Data are available for 24 women (placebo, n=12; low-dose, n=8; high-dose n=4). A6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received A6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the A6 groups compared with placebo (p=0.02). CONCLUSIONS: A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.

Original language	English
Journal	Gynecologic Oncology
Volume	111
Issue number	1
Pages (from-to)	89-94
Number of pages	6
ISSN	0090-8258
DOIs	https://doi.org/10.1016/j.ygyno.2008.06.028
Publication status	Published - 2008

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Ghamande, S. A., Silverman, M. H., Huh, W., Behbakht, K., Ball, G., Cuasay, L., Würtz, S. Ø., Brunner, N., & Gold, M. A. (2008). A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer. Gynecologic Oncology, 111(1), 89-94. https://doi.org/10.1016/j.ygyno.2008.06.028

A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer. / Ghamande, Sharad A.; Silverman, Michael H.; Huh, Warner et al.

In: Gynecologic Oncology, Vol. 111, No. 1, 2008, p. 89-94.

Research output: Contribution to journal › Journal article › Research › peer-review

Ghamande, SA, Silverman, MH, Huh, W, Behbakht, K, Ball, G, Cuasay, L, Würtz, SØ, Brunner, N & Gold, MA 2008, 'A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer', Gynecologic Oncology, vol. 111, no. 1, pp. 89-94. https://doi.org/10.1016/j.ygyno.2008.06.028

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title = "A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous {\AA}6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer",

abstract = "OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian cancer. METHODS: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose A6 (150 mg), or high-dose A6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of A6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. RESULTS: Data are available for 24 women (placebo, n=12; low-dose, n=8; high-dose n=4). A6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received A6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the A6 groups compared with placebo (p=0.02). CONCLUSIONS: A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.",

author = "Ghamande, {Sharad A.} and Silverman, {Michael H.} and Warner Huh and Kian Behbakht and Greg Ball and Luceli Cuasay and W{\"u}rtz, {Sidse {\O}rnbjerg} and Nils Brunner and Gold, {Michael A.}",

note = "Keywords: Adult; Aged; Aged, 80 and over; CA-125 Antigen; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Double-Blind Method; Fallopian Tube Neoplasms; Female; Humans; Injections, Subcutaneous; Middle Aged; Ovarian Neoplasms; Peptide Fragments; Peritoneal Neoplasms; Placebos; Prospective Studies; Receptors, Cell Surface; Urinary Plasminogen Activator",

year = "2008",

doi = "10.1016/j.ygyno.2008.06.028",

language = "English",

volume = "111",

pages = "89--94",

journal = "Gynecologic Oncology",

issn = "0090-8258",

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TY - JOUR

T1 - A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

AU - Ghamande, Sharad A.

AU - Silverman, Michael H.

AU - Huh, Warner

AU - Behbakht, Kian

AU - Ball, Greg

AU - Cuasay, Luceli

AU - Würtz, Sidse Ørnbjerg

AU - Brunner, Nils

AU - Gold, Michael A.

N1 - Keywords: Adult; Aged; Aged, 80 and over; CA-125 Antigen; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Double-Blind Method; Fallopian Tube Neoplasms; Female; Humans; Injections, Subcutaneous; Middle Aged; Ovarian Neoplasms; Peptide Fragments; Peritoneal Neoplasms; Placebos; Prospective Studies; Receptors, Cell Surface; Urinary Plasminogen Activator

PY - 2008

Y1 - 2008

N2 - OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian cancer. METHODS: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose A6 (150 mg), or high-dose A6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of A6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. RESULTS: Data are available for 24 women (placebo, n=12; low-dose, n=8; high-dose n=4). A6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received A6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the A6 groups compared with placebo (p=0.02). CONCLUSIONS: A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.

AB - OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian cancer. METHODS: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose A6 (150 mg), or high-dose A6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of A6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. RESULTS: Data are available for 24 women (placebo, n=12; low-dose, n=8; high-dose n=4). A6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received A6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the A6 groups compared with placebo (p=0.02). CONCLUSIONS: A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.

U2 - 10.1016/j.ygyno.2008.06.028

DO - 10.1016/j.ygyno.2008.06.028

M3 - Journal article

C2 - 18760451

SN - 0090-8258

VL - 111

SP - 89

EP - 94

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 1

ER -