Chlorophyllin Tablets for Urinary Bleeding Following Radiation Therapy for Cancers of Pelvic Organs (CLARITY)

April 26, 2022 updated by: Dr Gagan Prakash, Tata Memorial Centre

A Phase II Study to Evaluate Oral Chlorophyllin in Hemorrhagic Cystitis Secondary to Radiation Therapy for Pelvic Malignancies

To assess the efficacy of oral chlorophyllin tablets for urinary bleeding following radiation therapy for cancers of pelvic organs.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Radiation therapy to the pelvis is a commonly used treatment modality for urological, gynaecological and rectal cancers. Intensity modulation and image guidance have improved the delivery of radiation therapy in recent times. However, this does not eliminate the risk of radiation-induced damage to the adjacent healthy tissue - in this consideration, the bladder. Hemorrhagic cystitis accounts for 5-7% of emergency urology admissions. The procedure for the management of radiation cystitis proceeds from non-invasive oral drugs and HBOT to minimally invasive treatment like intravesical therapy and angioembolization, to more morbid procedures like cystectomy and urinary diversion. Although these treatment modalities have shown some success, most patients continue to have recurrent/persistent hematuria. There is a need to explore options of other oral/intravesical agents which can aid in mucosal healing and stop hematuria with lasting effects. Sodium-copper-chlorophyllin (CHL) is a phytopharmaceutical drug obtained from green plant pigment, chlorophyll. It is a semi-synthetic mixture of sodium copper salts derived from chlorophyll. Chlorophyllin scavenges radiation-induced free radicals and reactive oxygen species. Research at BARC has shown that chlorophyllin prevents radiation-induced toxicity in normal hematopoietic tissues and normal epithelial cells. A phase 1 clinical study in healthy volunteers indicate that CHL is safe and tolerable in humans and has not shown any severe adverse events. The purpose of this study is to evaluate the safety and efficacy of oral sodium copper chlorophyllin in hemorrhagic cystitis secondary to radiation therapy for pelvic malignancy.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Recruiting
        • Tata Memorial Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dr. Gagan Prakash
        • Sub-Investigator:
          • Dr. Vedang Murthy
        • Sub-Investigator:
          • Dr. Amit Joshi
        • Sub-Investigator:
          • Dr. Mahendra Pal
        • Sub-Investigator:
          • Dr. Priyamvada Maitre
        • Sub-Investigator:
          • Dr. Supriya Sastri
        • Sub-Investigator:
          • Dr. Santosh Menon
        • Sub-Investigator:
          • Dr. Nilesh Sable
        • Sub-Investigator:
          • Dr. Aparna Katdare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients ≥ 18 years of age with a history of radiotherapy for pelvic malignancy in the past more than 3 months back.
  • Any grade of radiation-induced cystitis as per RTOG criteria (RTOG Grade 1-4 equivalent to CTCAE Grade 1-3).
  • Adequate liver function defined as ALT/ALT ≤ 3 times ULN and total bilirubin ≤ 2 times ULN. Elevated transaminases up to 5 times ULN is allowed in patients with liver metastasis.
  • Adequate renal function defined as creatine clearance ≥ 30 mL/min (By Cockcroft-Gault formula).

Exclusion Criteria:

  • Known hypersensitivity or contraindications against sodium chlorophyllin.
  • Hemodynamically unstable patients not responding to initial resuscitation.
  • Patients with life-threatening hemorrhagic cystitis requiring urgent invasive intervention (CTCAE grade 4).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Chlorophyllin arm
Participants will receive oral Sodium Copper Chlorophyllin at a dose of 750mg once daily (OD) on an empty stomach.
Drug: Sodium Copper Chlorophyllin
Sodium-copper-chlorophyllin (CHL) is a phytopharmaceutical drug obtained from green plant pigment, chlorophyll. Chlorophyllin scavenges radiation-induced free radicals and reactive oxygen species. It is used as a food colorant and OTC in the USA, Japan, Australia and China for many years for a variety of health benefits including prevention of body odour in geriatric patients, enhanced wound healing, antibacterial action, prevention of cancer in the high-risk populations exposed to hepatocarcinogen aflatoxin B1, treatment of faecal incontinence etc. Studies have shown that CHL has immunostimulatory, anti-inflammatory and antiviral effects in addition to antioxidant and radioprotective properties. It increases the expression of a transcription factor (protein) Nrf2 which improves lymphocyte survival and enables efficient detoxification after exposure to radiation. The duration of therapy will be up to 6 months depending upon the response of participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.
Time Frame: Baseline
Objective Response Rate (ORR) The proportion of patients with CR/PR.The ORR will be determined as below.Complete response(CR):resolution of hematuria (gross/macroscopic hematuria for grade II/III and microscopic hematuria for grade I hemorrhagic cystitis) Partial response(PR):improvement (decrease by at least 1 grade of hemorrhagic cystitis but not complete resolution of hematuria over 3 months from the start of treatment.The grading of hemorrhagic cystitis will be as per the CTCAE v5.0.
Baseline
Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.
Time Frame: Post 1 month
Objective Response Rate (ORR) The proportion of patients with CR/PR.The ORR will be determined as below.Complete response(CR):resolution of hematuria (gross/macroscopic hematuria for grade II/III and microscopic hematuria for grade I hemorrhagic cystitis) Partial response(PR):improvement (decrease by at least 1 grade of hemorrhagic cystitis but not complete resolution of hematuria over 3 months from the start of treatment.The grading of hemorrhagic cystitis will be as per the CTCAE v5.0.
Post 1 month
Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.
Time Frame: Post 3 months
Objective Response Rate (ORR) The proportion of patients with CR/PR.The ORR will be determined as below.Complete response(CR):resolution of hematuria (gross/macroscopic hematuria for grade II/III and microscopic hematuria for grade I hemorrhagic cystitis) Partial response(PR):improvement (decrease by at least 1 grade of hemorrhagic cystitis but not complete resolution of hematuria over 3 months from the start of treatment.The grading of hemorrhagic cystitis will be as per the CTCAE v5.0.
Post 3 months
Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.
Time Frame: Post 6 months
Objective Response Rate (ORR) The proportion of patients with CR/PR.The ORR will be determined as below.Complete response(CR):resolution of hematuria (gross/macroscopic hematuria for grade II/III and microscopic hematuria for grade I hemorrhagic cystitis) Partial response(PR):improvement (decrease by at least 1 grade of hemorrhagic cystitis but not complete resolution of hematuria over 3 months from the start of treatment.The grading of hemorrhagic cystitis will be as per the CTCAE v5.0.
Post 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Bladder Cancer Index (BCI) scores.
Time Frame: Baseline, post 1 month, post 3 months

Bladder cancer index (BCI) scores will be calculated at baseline, 1 month and 3 months for each study participant.

Minimum value - 0, Maximum value - 100, Higher scores depict better outcome.
Baseline, post 1 month, post 3 months
Assessment of Treatment Failure (TF).
Time Frame: Post 3 months
Treatment Failure (TF) defined as requirement of alternative intervention for persistent severe hematuria within 3 months from the start of treatment or early stoppage due to intolerable side effects in the absence of PR/CR [Intervention: multiple cystoscopies with clot evacuation, cystectomy, hyperbaric oxygen therapy (HBOT) or transfusion due to persistent drop in hemoglobin].
Post 3 months
Evaluation of treatment failure-free survival.
Time Frame: Baseline to up to 3 months
Treatment failure-free survival is defined as the time from enrolment to the date of first intervention up to 3 months or date of discontinuation of therapy due to intolerable side effects in the absence of PR/CR.
Baseline to up to 3 months
Assessment of Quality of Life (QOL) using EORTC -QLQ C-30 questionnaire.
Time Frame: Baseline, post 1 month, post 3 months

QoL will be measured using the EORTC-QLQ-30 questionnaire at baseline, 1 month and 3 months for each study participant.

Minimum value - 0, Maximum value cannot be predetermined. five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Therefore, higher scores depict better outcomes for some scales whereas for some scales lower scores depict better outcomes.
Baseline, post 1 month, post 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Collaborators

Bhabha Atomic Research Centre (BARC), Mumbai

Investigators

  • Principal Investigator: Dr. Gagan Prakash, Tata Memorial Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2022

Primary Completion (Anticipated)

March 31, 2024

Study Completion (Anticipated)

March 31, 2024

Study Registration Dates

First Submitted

March 17, 2022

First Submitted That Met QC Criteria

April 26, 2022

First Posted (Actual)

April 27, 2022

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 26, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 900878

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All study-related information will be strictly maintained and will be shared only with the IEC and DSMB authorities.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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