Highlight
- PRO-PLATINUM is a prospective, randomized, double-blind, placebo-controlled trial assessing the impact of a 5-strain probiotic intervention on the gut and vaginal microbiome during platinum-based chemotherapy for ovarian cancer (OC).
- The study enrolls patients with advanced or platinum-sensitive recurrent high-grade OC, randomizing them to probiotic or placebo arms, and collects biospecimens for metagenomic, metabolomic, immunologic, and microbiome analyses.
- Primary endpoint focuses on gut microbiome compositional changes, while secondary and exploratory endpoints assess treatment adherence, survival outcomes, toxicity, quality of life, and microbiome correlations with clinical response.
- The trial seeks to establish the biological plausibility and clinical feasibility of microbiome-directed interventions to improve chemotherapy tolerance and outcomes in OC patients.
Study Background
Ovarian cancer remains a leading cause of gynecologic cancer mortality worldwide, characterized by late-stage diagnosis and frequent chemotherapy resistance. Platinum-based chemotherapy is the standard frontline and recurrent treatment; however, dose-limiting toxicities and variable treatment response often limit efficacy. Recent research implicates the gut microbiome as a key modulator of chemotherapeutic drug metabolism, host immunity, and therapy-related toxicity. Alterations in microbial diversity and composition during chemotherapy may influence patient outcomes and adverse effect profiles. Probiotic supplementation to favorably modulate the microbiome represents an emerging strategy to enhance treatment tolerance and efficacy. Despite promising preclinical data, robust clinical trials in OC investigating microbiome interventions remain sparse. PRO-PLATINUM addresses this unmet need by formally evaluating a defined multispecies probiotic formulation during platinum chemotherapy in a rigorous clinical framework.
Study Design
PRO-PLATINUM is an Institutional Review Board–approved, randomized, double-blind, placebo-controlled trial initiated in February 2026, enrolling 124 patients diagnosed with stage II-IV or platinum-sensitive recurrent high-grade ovarian cancer undergoing platinum-based chemotherapy. Participants are randomized 1:1 to receive either the probiotic intervention WBF-038 or placebo, stratified by newly diagnosed advanced versus recurrent disease status.
The probiotic formulation contains inulin, a prebiotic fiber, plus five bacterial strains: Akkermansia muciniphila, Anaerobutyricum hallii, Clostridium beijerinckii, Clostridium butyricum, and Bifidobacterium infantis. The intervention is orally administered twice daily, starting within seven days of the first chemotherapy cycle and continuing through seven days after the completion of cycle six.
Eligibility criteria include Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and adequate organ function, excluding patients with contraindications to probiotic administration. Comprehensive biospecimens—stool, blood, vaginal swabs—are collected at baseline, mid-therapy (cycle 3), and end of treatment (cycle 6), with tumor tissue acquired during surgery when possible.
Primary endpoint is the change in gut microbiome composition, assessed by whole-genome metagenomic sequencing. Secondary endpoints encompass intervention adherence, biospecimen collection feasibility, recurrence-free survival, and overall survival. Exploratory endpoints evaluate chemotherapy toxicity profiles, postoperative infections, stool consistency, diet, concurrent medications, antibiotic exposure, quality of life metrics, symptom burden, serum metabolomics, immune profiling, vaginal and tumor microbiome analyses, plus correlations of microbial features with clinical outcomes.
Key Findings
As of the current report, enrollment is underway with preliminary data collection ongoing. While mature clinical endpoints remain forthcoming, expected results include detailed characterization of gut microbiome dynamics in response to platinum chemotherapy and probiotic supplementation.
The study aims to determine if the probiotic significantly alters gut microbial diversity or the relative abundance of beneficial taxa associated with immune regulation and chemotherapeutic metabolism. Secondary analyses will examine adherence rates and the practical feasibility of frequent biospecimen collection in this population, as well as signals regarding reduced toxicity or improved quality of life.
Emerging correlative data will explore metabolomic and immune biomarkers that may mediate microbiome effects on chemotherapy response or toxicity. Of particular interest are shifts in vaginal microbiome composition, given potential implications for pelvic infection rates and mucosal immunity.
Future full analysis will provide effect sizes with confidence intervals for microbiome compositional change and survival outcomes, addressing the clinical relevance of probiotic adjuncts during chemotherapy.
Expert Commentary
The PRO-PLATINUM study represents an important advancement in the translation of microbiome science to clinical oncology practice. By focusing on a well-defined probiotic blend designed to enrich taxa implicated in mucosal barrier integrity and immune homeostasis, this trial moves beyond observational microbiome studies towards actionable interventions.
Nonetheless, limitations include the complexity of host-microbe-drug interactions and variability in diet or antibiotic use that may confound probiotic effects. Generalizability to broader OC populations, including those with poor performance status or platinum-resistant disease, remains to be established.
Mechanistically, modulation of short-chain fatty acid producers (e.g., Clostridium butyricum) could enhance host immunity and mitigate gastrointestinal toxicity, aligning with evolving paradigms linking the microbiome to systemic cancer therapy outcomes.
Conclusion
PRO-PLATINUM is pioneering the rigorous clinical evaluation of probiotic supplementation as an adjunct to platinum chemotherapy in ovarian cancer. By integrating comprehensive microbiome, immune, and metabolic profiling with clinical endpoints, it aims to elucidate pathways to improve treatment tolerance, quality of life, and oncologic outcomes. This translational effort could catalyze new microbiome-directed therapeutic strategies in gynecologic oncology and set a precedent for integrating microbiome modulation into standard cancer care.
Funding and ClinicalTrials.gov
The study was supported by institutional funding and grants associated with the clinical trial infrastructure. PRO-PLATINUM is registered at ClinicalTrials.gov under the identifier NCTXXXXXXX (identifier not specified in the original abstract).
References
1. Chambers LM, Spakowicz D, Chalif J, et al. PRO-PLATINUM: A randomized, double-blind, placebo controlled study to investigate the efficacy of a probiotic intervention on the gut and vaginal microbiome of ovarian cancer patients undergoing treatment with platinum chemotherapy. Gynecol Oncol. 2026 Jun 27;211:74-78. PMID: 42364424.
2. Zitvogel L, Daillère R, Roberti MP, Routy B, Kroemer G. Anticancer effects of the microbiome and its products. Nat Rev Microbiol. 2017 Aug;15(8):465-478.
3. Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 2018 Jan 5;359(6371):104-108.
4. Alexander JL, Wilson ID, Teare J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):715-727.
