Concomitant Curcumin Palliative Radiotherapy in Advanced Cervical Cancer Trial (CuPRAC)

Feasibility, Safety, and Efficacy of Concomitant Curcumin in Patients Undergoing Palliative Radiotherapy for FIGO Stage IIIB-IVA Cervical Cancer: An Open-label Pilot Trial

The goal of this clinical trial is to test curcumin as an adjunct treatment in patients with cervical cancer receiving standard-of-care palliative radiation. The main questions it aims to answer are:

1. Is adding curcumin to standard-of-care palliative radiotherapy of cervical cancer patients feasible? Is conducting this study feasible?
2. Does adding curcumin to standard-of-care palliative radiotherapy of cervical cancer patients improve therapeutic responses?
3. Is adding curcumin to standard-of-care palliative radiotherapy of cervical cancer patients safe?
4. How much curcumin is absorbed into the body and how long will it stay in the body?

Participants will:

i. Take 250 mg curcumin capsules four times per day for 4-6 weeks in addition to the prescribed palliative radiotherapy.

ii. Provide blood and urine samples for laboratory tests. iii. Provide blood samples to measure curcumin levels in their body. iv. Obtain CT-scan to measure their tumor response. v. Complete questioners to measure improvements to their quality of life, if any.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Curcumin; Radiation: Palliative radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Biniyam Girma, Bpharm, MSc; Phone Number: 251 093-708-9518; Email: biniyam.girma@ju.edu.et
• Study Contact Backup: Name: Michele Joseph, MSc, MPH; Phone Number: 251 092-914-2593; Email: michele.joseph@aau.edu.et

Study Locations

• Ethiopia
  • Addis Ababa, Ethiopia
    • Recruiting
    • Tikur Anbessa Specialized Hospital
    • Contact: Wondemagegnehu Tignehe, MD; Email: tigeneh@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age >18 years old (Adult, Older Adult)
• Histologically confirmed squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix, FIGO stage IIIB-IVA
• Undergoing for standard of care palliative radiotherapy without chemotherapy as per the local treatment guideline
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
• Adequate liver function (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (Upper Limit of Normal); total serum bilirubin ≤1.5 x ULN); blood cell counts (absolute neutrophils count ≥1.500/mm3; platelet count ≥100.000/mm3; hemoglobin ≥10.0 g/dL); renal function (serum creatinine ≤1.5 x ULN; estimate creatinine clearance (Cockcroft-Gault) ≥60 mL/min)
• Participants must have measureable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1.
• Agree to use an effective form of contraception (e.g., true abstinence (not periodic abstinence), barrier contraception, highly effective hormonal contraception) if the participant is of child bearing age
• Give informed consent

Exclusion criteria:

• Cervical cancer patients who are candidates for single dose palliative radiotherapy
• Patients with severe or bilateral hydronephrosis
• Evidence of distant metastases
• Receiving any other investigational agent concurrently or within the last 4 weeks before enrollment
• Received any previous radiation or chemotherapy for cervical cancer
• Underwent surgery in the four weeks prior to the enrolment date or scheduled to undergo surgery within eight weeks after end of treatment
• Currently using of any chemotherapy or scheduled to receive within eight weeks after end of treatment
• Known allergy to turmeric or its derivatives (ginger, curry, cumin, or cardamom)
• Known allergy to fenugreek, peanut, soy, lentil, pea, bean, and chickpea
• Presence of conditions that precludes the safe administration of the trial intervention and/or prohibit adequate compliance to study requirements including chronic ongoing infections (like HIV, Hepatitis B or C), uncontrolled hypertension, heart failure, cardiac arrhythmia, unstable angina, chronic obstructive lung disease, diabetes mellitus, chronic renal disease, chronic liver disease, biliary tract obstruction or cholelithiasis, gastric or duodenal ulcers, autoimmune or inflammatory disorders, a coagulation or platelet disorder, seizure disorders and psychiatric illness. Patients with disorders other than the ones specified above may also be excluded based on the judgment of the principal investigator.
• Pregnant and breastfeeding women
• Participants with circumstances that will not permit completion of the study or required follow-up. For instance, if travel to and from treatment site is an issue.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Concurrent Curcumin Palliative Radiotherapy; Daily 1000 mg oral CGM Curcumin in four divided doses for seven days prior to the start of and for three to five weeks concurrently with palliative radiotherapy.

Drug: Curcumin; Curcumin formulation with enhanced bioavailability which contains food-grade curcumin 35% (w/w) combined with the galactomannan fiber from fenugreek seeds.; Other Names: Curcumagalactomannoside (CGM); CurQfen; Radiation: Palliative radiotherapy; As per the treatment guidelines of the Tikur Anbessa Hospital Radiotherapy Center, standard-of-care palliative or non-radical radiotherapy entails treatment of advanced cervical cancer patients at a biologically effective dose of 45-55 Gy over the course of three to five weeks.; Other Names: Non-radical radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate is defined as proportion of participants having a complete response (CR) or partial response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Time Frame: 13-17 weeks
Treatment Fidelity Rate	Proportion of participants who received the study treatment as planned	From initiation (Day 1) up to end of treatment over 4-6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Dose Intensity (RDI) of curcumin and radiotherapy	Relative dose intensity is defined as dose intensity (actual DI) divided by the protocol weekly dose (planned DI), expressed as a percentage.	From initiation (Day 1) up to end treatment over 4-6 weeks
Disease Control Rate (DCR)	Disease control rate (DCR): proportion of participants having a complete response (CR) or partial response (PR) or stable disease (SD) as defined by the RECIST 1.1 criteria.	13-17 weeks
Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-C30 at 7-9 weeks	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) measures quality of life in cancer patients by evaluating physical, psychological, and social functions. Possible scores range from zero to 100, with a higher scale score indicating a higher response level. As such, high scores on functional and global health status (QoL) scales indicate healthy levels of functioning and high quality of life, respectively. However, a high score on the symptoms scale or item indicates more problems or symptomatology.	Baseline, 7-9 weeks
Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-C30 at 13-17 weeks	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) measures quality of life in cancer patients by evaluating physical, psychological, and social functions. Possible scores range from zero to 100, with a higher scale score indicating a higher response level. As such, high scores on functional and global health status (QoL) scales indicate healthy levels of functioning and high quality of life, respectively. However, a high score on the symptoms scale or item indicates more problems or symptomatology.	Baseline, 13-17 weeks
Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-CX24 at 7-9 weeks	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module (EORTC QLQ-CX24) measures quality of life in cervical cancer patients in combination with the QLQ-C30. Possible scores range from zero to 100 for all scale and single-item measures. While a high score on the functional single-items indicates a high degree of functioning, a high score on the symptom scales or single-items indicates a high level of symptomatology or difficulties.	Baseline, 7-9 weeks
Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-CX24 at 13-17 weeks	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module (EORTC QLQ-CX24) measures quality of life in cervical cancer patients in combination with the QLQ-C30. Possible scores range from zero to 100 for all scale and single-item measures. While a high score on the functional single-items indicates a high degree of functioning, a high score on the symptom scales or single-items indicates a high level of symptomatology or difficulties.	Baseline, 13-17 weeks
Recruitment Rate	Recruitment Rate is defined as the proportion of those who participate in the trial who were approached as potential participants.	through study completion, an average of 1 year
Assessment Completion Rate	Assessment Completion Rate is defined as the proportion of assessments that could be completed as planned.	through study completion, an average of 1 year
Attrition Rate	Attrition Rate is defined as the proportion of participants who withdraw from the study.	through study completion, an average of 1 year
Incidence of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	Any new or worsening of a pre-existing untoward sign, symptom, or disease, including a clinically significant laboratory or vital sign abnormality during study treatment, is defined as a treatment emergent adverse event	Up to 10-14 weeks from treatment initiation
Incidence of Dose Reduction in curcumin and radiotherapy regimens	Incidence of Dose A dose reduction is a decrease in dose from the protocol planned starting dose or a decrease from the previous non-zero dose, even if this decrease has been directly preceded by an interruption in curcumin and radiotherapy regimens	: From initiation (Day 1) up to end treatment over 4-6 weeks
Incidence of Dose Interruption in curcumin and radiotherapy regimens	A Dose Interruption is defined a zero dose given on one or more days on which the protocol-specified dose is non-zero, followed by resumption of dosing	From initiation (Day 1) up to end treatment over 4-6 weeks
Dose Intensity (DI) of curcumin and radiotherapy	Dose intensity is defined as cumulative dose divided by the treatment duration in weeks	From initiation (Day 1) up to end treatment over 4-6 weeks
Peak Plasma Concentration (Cmax) of CGM Curcumin	Peak Plasma Concentration represents the highest observed curcumin concentration observed in plasma over all PK sample concentrations following single-dose CGM Curcumin administration.	Day 1: pre-dose, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours and 6 hours post-dose; Day 6: 30 minutes before the next daily dose, and 1 hour post- dose
Time to Peak Plasma Concentration (Tmax) of CGM Curcumin	Time to Peak Plasma Concentration (Tmax) represents the time when Cmax of curcumin occurs following single-dose CGM Curcumin administration.	Day 1: pre-dose, 30 minutes, 1 hour, 1.5 hours, 2hours, 4 hours and 6 hours post-dose; Day 6: 30 minutes before the next daily dose, and 1 hour post- dose
Area under the Plasma Concentration versus Time Curve (AUCτ) of CGM Curcumin	Area under the Plasma Concentration versus Time Curve (AUCτ) represents the area under the concentration-time curve of curcumin from time zero to the time of the end of dosing interval following single-dose CGM Curcumin administration.	Day 1: pre-dose, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours and 6 hours post-dose; Day 6: 30 minutes before the next daily dose, and 1 hour post- dose
Half-life (T1/2) of CGM Curcumin	Half-life (T1/2) represents the time for plasma concentration of curcumin to fall by a factor of one-half in the terminal phase following single-dose CGM Curcumin administration.	Day 1: pre-dose, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours and 6 hours post-dose; Day 6: 30 minutes before the next daily dose, and 1 hour post- dose

Collaborators and Investigators

• Sponsor: Addis Ababa University
• Collaborators: Center for Innovative Drug Development and Therapeutic Trials for Africa, Addis Ababa University; Akay Natural Ingredients Private Limited
• Investigators: Study Chair: Eyasu Makonnen, Bpharm, PhD, Addis Ababa University; Study Director: Biniyam Girma, Bpharm, MSc, Addis Ababa University; Principal Investigator: Wondemagegnehu Tigeneh, MD, MMed(RT), Addis Ababa University

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Curcumin; Cervical cancer; Radiosensitizer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Curcumin
• Other Study ID Numbers: 001/21/SoP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No