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

Phase 2

• Conditions: Hemorrhagic Cystitis
• Interventions: Drug: Sodium Copper Chlorophyllin

• Registration Number: NCT05348239
• Lead Sponsor: Tata Memorial Centre

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-03-17
• Study Start: 2022-03-26
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-26
• Last Update Submitted: 2022-04-26
• Study First Posted: 2022-04-27
• Last Update Posted: 2022-04-27
• Primary Completion: 2024-03-31
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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).

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral Chlorophyllin arm	Sodium Copper Chlorophyllin	Participants will receive oral Sodium Copper Chlorophyllin at a dose of 750mg once daily (OD) on an empty stomach.

Primary Outcome Measures

Name	Time	Method
Assessment of Objective Response Rate (ORR) as per CTCAE v5.0.	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.

Secondary Outcome Measures

Name	Time	Method
Assessment of Bladder Cancer Index (BCI) scores.	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.
Assessment of Treatment Failure (TF).	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 \[Intervention: multiple cystoscopies with clot evacuation, cystectomy, hyperbaric oxygen therapy (HBOT) or transfusion due to persistent drop in hemoglobin\].
Evaluation of treatment failure-free survival.	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.
Assessment of Quality of Life (QOL) using EORTC -QLQ C-30 questionnaire.	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.

Trial Locations

Locations (1)

Tata Memorial Centre; 🇮🇳 Mumbai, Maharashtra, India