Abstract CT219: Phase II trial of grape seed extract for localized prostate cancer with PSA progression after local therapy

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. Androgen deprivation therapy (ADT) is often used for patients with rising prostate specific antigen (PSA) levels after local treatment but is associated with morbidity and decreased quality of life. Patients with non-metastatic PSA progression after local therapy and a long PSA doubling time (PSADT) may have an extended observation period when monitoring PSA levels prior to starting ADT and other systemic therapies. This observation period provides an opportunity to investigate low-impact interventions. Grape seed extract (GSE) is a phytochemical which has shown promise given its tolerability and potential effect on PCa growth and progression. Herein, we report the results of a completed Phase II clinical trial (CT.gov-NCT03087903) which investigated the effect of oral GSE in patients with PSA-only recurrence after maximum local therapy for PCa. GSE was administered as a Leucoselect Phytosome-Indena S.p.A. formulation which contained ∼100% proanthocyanidins, enriched in lower procyanidin oligomers complexed with soy phospholipids, in the ratio 1:2.6 w/w (to increase GSE bioavailability). Eligible patients had a PSA ≥ 0.2 ng/mL and evidence of rising PSA, on 2 separate occasions, at least one week apart. Study endpoints included PSA response (defined as a ≥ 30% increase in PSADT) and change in PSA velocity. PSA levels were checked at baseline, 6 weeks and 3, 6, 9, and 12 months after starting GSE. Forty-one patients were given 150mg of GSE orally twice daily for 12 months or until PSADT ≤3 months. PSADT increased with GSE intervention from 5.71 months at screening to 6.86 months post treatment (p <0.001). Notably, 32 patients of 41 (78%) had an increase in their PSADT, with 15 (37%) of those patients meeting the primary endpoint of a ≥ 30% increase. Nine (22%) patients showed a decrease in PSADT. Interestingly, patients with increased PSADT had higher baseline PSA (average ∼1.9 vs. 0.7 ng/mL) and testosterone levels (average ∼3.73 vs. 2.28 ng/mL), at screening, compared to patients in the decreased PSADT response group. GSE was well tolerated with only one patient discontinuing treatment due to hypertension and rash. In conclusion, GSE may delay progression of prostate cancer based on impact of PSADT; PCa patients with increased baseline PSA and testosterone levels may be more responsive to GSE intervention. Confirmation of its benefits are necessary in larger patient cohorts (placebo-controlled trials). This work was supported by NCI P30 CA046934 Cancer Center Support Grant, Cancer League of Colorado, the Diane D. Writer Foundation, and the Barbara and Richard Gardner Fund for Prostate Cancer Research. Citation Format: Paul Maroni, Tad Manalo, Elizabeth R. Kessler, Andrew Nicklawsky, Victor Trevisanut, Thomas W. Flaig, Elaine T. Lam, Dexiang Gao, Komal Raina, Rajesh Agarwal. Phase II trial of grape seed extract for localized prostate cancer with PSA progression after local therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT219.