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

• ClinicalTrials.gov Identifier: NCT05947513
• Recruitment Status: Not yet recruiting
• First Posted: July 17, 2023
• Last Update Posted: July 17, 2023
• Sponsor: Addis Ababa University
• Collaborators: Center for Innovative Drug Development and Therapeutic Trials for Africa, Addis Ababa University; Akay Natural Ingredients Private Limited
• Information provided by (Responsible Party): Biniyam Girma, Addis Ababa University

Study Description

Brief Summary:

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:

• Is adding curcumin to standard-of-care palliative radiotherapy of cervical cancer patients safe?
• Does adding curcumin to standard-of-care palliative radiotherapy of cervical cancer patients improve therapeutic responses?
• How much curcumin is absorbed into the body and how long will it stay in the body?

Participants will:

• Take two 500 mg curcumin capsules twice per day for 4-6 weeks in addition to the prescribed palliative radiotherapy.
• Provide blood and urine samples for laboratory tests.
• Provide blood samples to measure curcumin levels in their body.
• Obtain CT-scan to measure their tumor response.
• Complete questioners to measure improvements to their quality of life, if any.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer	Drug: Curcumin; Radiation: Palliative radiotherapy	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Feasibility, Safety, and Efficacy of Concomitant Curcumin in Patients Undergoing Palliative Radiotherapy for FIGO Stage IIIB-IVA Cervical Cancer: An Open-label Pilot Trial
• Estimated Study Start Date: October 2023
• Estimated Primary Completion Date: November 2024
• Estimated Study Completion Date: November 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: Concurrent Curcumin Palliative Radiotherapy; Daily 1000 mg oral CGM Curcumin in two 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 Name: Non-radical radiotherapy

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants without treatment-related toxicities leading to premature termination of treatment [ Time Frame: From initiation (Day 1) up to end of treatment over 4-6 weeks ]
2. Objective Response Rate (ORR) [ Time Frame: Time Frame: 13-17 weeks ]
   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.
3. Incidence of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [ Time Frame: Up to 10-14 weeks from treatment initiation ]
   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.
4. Incidence of Dose Interruption in curcumin and radiotherapy regimens [ Time Frame: From initiation (Day 1) up to end treatment over 4-6 weeks ]
   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.
5. Incidence of Dose Reduction in curcumin and radiotherapy regimens [ Time Frame: From initiation (Day 1) up to end treatment over 4-6 weeks ]
   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.
6. Dose Intensity (DI) of curcumin and radiotherapy [ Time Frame: From initiation (Day 1) up to end treatment over 4-6 weeks ]
   Dose intensity is defined as cumulative dose divided by the treatment duration in weeks.
7. Relative Dose Intensity (RDI) of curcumin and radiotherapy [ Time Frame: From initiation (Day 1) up to end treatment over 4-6 weeks ]
   Relative dose intensity is defined as dose intensity (actual DI) divided by the protocol weekly dose (planned DI), expressed as a percentage.

Secondary Outcome Measures :

1. Disease Control Rate (DCR) [ Time Frame: 13-17 weeks ]
   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.
2. Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-C30 at 7-9 weeks [ Time Frame: Baseline, 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.
3. Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-C30 at 13-17 weeks [ Time Frame: Baseline, 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.
4. Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-CX24 at 7-9 weeks [ Time Frame: Baseline, 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.
5. Change from baseline in Health-Related Quality of Life (QOL) as assessed using EORTC QLQ-CX24 at 13-17 weeks [ Time Frame: Baseline, 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.
6. Peak Plasma Concentration (Cmax) of CGM Curcumin [ Time Frame: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose ]
   Peak Plasma Concentration represents the highest observed curcumin concentration observed in plasma over all PK sample concentrations following single-dose CGM Curcumin administration.
7. Time to Peak Plasma Concentration (Tmax) of CGM Curcumin [ Time Frame: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose ]
   Time to Peak Plasma Concentration (Tmax) represents the time when Cmax of curcumin occurs following single-dose CGM Curcumin administration.
8. Area under the Plasma Concentration versus Time Curve (AUCτ) of CGM Curcumin [ Time Frame: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose ]
   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.
9. Half-life (T1/2) of CGM Curcumin [ Time Frame: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose ]
   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.
10. Recruitment Rate [ Time Frame: through study completion, an average of 1 year ]
    Recruitment Rate is defined as the proportion of those who participate in the trial who were approached as potential participants.
11. Assessment Completion Rate [ Time Frame: through study completion, an average of 1 year ]
    Assessment Completion Rate is defined as the proportion of assessments that could be completed as planned.
12. Attrition Rate [ Time Frame: through study completion, an average of 1 year ]
    Attrition Rate is defined as the proportion of participants who withdraw from the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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 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.

Contacts and Locations

Contacts

Contact: Biniyam Girma, Bpharm, MSc; 093-708-9518 ext 251; biniyam.girma@ju.edu.et

Contact: Michele Joseph, MSc, MPH; 092-914-2593 ext 251; michele.joseph@aau.edu.et

Sponsors and Collaborators

Addis Ababa University

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

More Information

• Responsible Party: Biniyam Girma, Principal Investigator, Addis Ababa University
• ClinicalTrials.gov Identifier: NCT05947513
• Other Study ID Numbers: 001/21/SoP
• First Posted: July 17, 2023
• Last Update Posted: July 17, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biniyam Girma, Addis Ababa University:

Curcumin; Cervical cancer; Radiosensitizer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Curcumin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action