Study protocol for a randomized, double-blind, placebo-controlled clinical trial to assess chemoprotective efficacy of Aqueous standardized extract of Tinospora cordifolia (AsSET) in patients receiving Docetaxel based chemotherapy for advanced / meta

Introduction Docetaxel is widely used for advanced and metastatic solid tumours, but dose limiting toxicities, particularly haematological adverse events, often lead to treatment delays, dose reductions or discontinuation and impair quality of life. Tinospora cordifolia (Guduchi), long used in Ayurveda for its immunomodulatory and rejuvenating properties, has shown chemoprotective potential in experimental and early clinical studies, but robust randomized evidence is lacking. This trial evaluates whether adding an aqueous standardized extract of T. cordifolia(AsSET) to docetaxel-based chemotherapy reduces grade ≥2 adverse events and improves quality of life in patients with advanced or metastatic solid tumours. Methods and analysis This randomized, double-blinded, and placebo-controlled trial designed to evaluate the chemoprotective efficacy of an aqueous standardised extract of Tinospora cordifolia (AsSET) in patients with advanced, recurrent or metastatic solid tumors receiving docetaxel-based chemotherapy. A total of 81 eligible patients that have provided informed consent were recruited in the study. Participants were randomized 2:1 to AsSET or placebo using stratified permuted block randomization, stratified by planned cumulative docetaxel dose (≤ 225 vs >225 mg/m2), except five participants enrolled before that date were allocated by minimization. All participants received standard intravenous docetaxel-based chemotherapy plus oral administration of either AsSET (two 300mg tablets, 600mg, twice daily) or matching placebo, from enrolment until completion of docetaxel-based therapy. Clinical, laboratory, imaging, and questionnaire based-assessment were performed at baseline, at scheduled interval during treatment and at the final visit. In consenting participants, blood samples for pharmacokinetics were collected once, at nine timepoints up to 24 hours, in any chemotherapy cycle from cycle 2 onwards. Adverse events were graded according to CTCAE version 5.0. The primary outcome is the proportion of patients experiencing grade ≥2 adverse events from first dose to study completion (up to 24 weeks). Secondary outcomes include quality of life measured by the EORTC QLQ-C30 and the disease-site-specific FACT scale, progression-free survival (PFS) per RECIST v1.1, haematological and biochemical parameters, and pharmacokinetic parameters. The database was locked on 17 September 2026 and the locked dataset was transferred to an independent statistician who remains blinded to treatment allocation. Unblinding has not yet been done and outcome analysis has not started. Ethics and dissemination This study was approved by the Institutional Ethics Committee III (IEC) of the Advanced Centre for Treatment Research & Education in Cancer, Tata Memorial Centre, (ACTREC), Kharghar, Sector 22, Navi Mumbai (project approval no. 900950; first approved on 28 June 2023; this paper describes the most recently amended protocol, version 4.0 dated 24 February 2026; amendments are listed in Annexure 1). The trial is registered with the Clinical Trials Registry-India (CTRI/2023/08/056129) and is conducted in accordance with ICH Good Clinical Practice, the new drugs and Clinical Trials Rules 2019. All participants provided written informed consent, with an additional consent for pharmacokinetic sampling. Participants data are coded to protect confidentiality, and no participant will be identified in any publication without permission. The findings from this study will be presented at an academic conference and published in scholarly journals regardless of the findings.