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

• ClinicalTrials.gov Identifier: NCT05348239
• Recruitment Status: Recruiting
• First Posted: April 27, 2022
• Last Update Posted: April 27, 2022
• Sponsor: Tata Memorial Centre
• Collaborator: Bhabha Atomic Research Centre (BARC), Mumbai
• Information provided by (Responsible Party): Dr Gagan Prakash, Tata Memorial Centre

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hemorrhagic Cystitis	Drug: Sodium Copper Chlorophyllin	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A prospective, single centre, single-arm, interventional phase II study.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Evaluate Oral Chlorophyllin in Hemorrhagic Cystitis Secondary to Radiation Therapy for Pelvic Malignancies
• Actual Study Start Date: March 26, 2022
• Estimated Primary Completion Date: March 31, 2024
• Estimated Study Completion Date: March 31, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.

Secondary Outcome Measures :

1. 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.

2. 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].
3. 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.
4. 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.

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Dr. Gagan Prakash; 022 2417 ext 7176; gagan2311@gmail.com

Contact: Dr. Vikram Gota; +91 7715019117; vikramgota@gmail.com

Locations

India

Tata Memorial Centre; Recruiting

Mumbai, Maharashtra, India, 400012

Contact: Dr. Gagan Prakash 022 2417 ext 7176 gagan2311@gmail.com

Contact: Dr. Vikram Gota +91 7715019117 vikramgota@gmail.com

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

Sponsors and Collaborators

Tata Memorial Centre

Bhabha Atomic Research Centre (BARC), Mumbai

Investigators

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

More Information

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Interim Clinical Study Report (Project No. 0462-16) - An Open Label, Clinical Study To Assess Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Sodium Copper Chlorophyllin In Healthy Adult, Human Male Subjects.

• Responsible Party: Dr Gagan Prakash, Professor, Urologic Oncology, Tata Memorial Centre
• ClinicalTrials.gov Identifier: NCT05348239
• Other Study ID Numbers: 900878
• First Posted: April 27, 2022
• Last Update Posted: April 27, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: All study-related information will be strictly maintained and will be shared only with the IEC and DSMB authorities.

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

Additional relevant MeSH terms:

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Copper; Chlorophyllin; Trace Elements; Micronutrients; Physiological Effects of Drugs; Antimutagenic Agents; Protective Agents