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

Hemorrhagic Cystitis Clinical Trial

— CLARITY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05348239
• Other study ID #: 900878
• Status: Recruiting
• Phase: Phase 2
• Start date: March 26, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: April 2022
• Source: Tata Memorial Centre
• Contact: Dr. Gagan Prakash
• Phone: 022 2417
• Email: gagan2311[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Cystitis
• Hemorrhagic Cystitis

Intervention

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.

Locations

Country	Name	City	State
India	Tata Memorial Centre	Mumbai	Maharashtra

Sponsors (2)

Lead Sponsor	Collaborator
Tata Memorial Centre	Bhabha Atomic Research Centre (BARC), Mumbai

Country where clinical trial is conducted

India, 

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.	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
Primary	Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.	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
Primary	Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.	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
Primary	Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.	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	Assessment of Bladder Cancer Index (BCI) scores.	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
Secondary	Assessment of Treatment Failure (TF).	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
Secondary	Evaluation of treatment failure-free survival.	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
Secondary	Assessment of Quality of Life (QOL) using EORTC -QLQ C-30 questionnaire.	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