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Hemorrhagic CystitisPhase 2CLARITYNCT05348239

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

A Phase 2 study testing Sodium Copper Chlorophyllin in people with Hemorrhagic Cystitis, run by Tata Memorial Centre at 1 site in India.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To assess the efficacy of oral chlorophyllin tablets for urinary bleeding following radiation therapy for cancers of pelvic organs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hemorrhagic Cystitis
What is being tested?
Sodium Copper Chlorophyllin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteIndia
Study dates
26 Mar 2022to 31 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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).

Trial locations and contacts

1 site in 1 country.

Dr. Gagan Prakash contact

022 2417 ext. 7176

gagan2311@gmail.com

Dr. Vikram Gota contact

+91 7715019117

vikramgota@gmail.com

India1 site, 1 recruiting
  • Tata Memorial Centre

    Mumbai, Maharashtra, 400012

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

    Dr. Vikram Gota, +91 7715019117, vikramgota@gmail.com

    Recruiting

Other trials in India

About this study

Official title: 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.

Read the 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.

Being tested
Sodium Copper Chlorophyllin
Medical subject headings
Cystitis, Hemorrhagic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium Copper ChlorophyllinDrug

    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.

Study groups in NCT05348239
Study groupRoleWhat they receive
Oral Chlorophyllin armExperimentalParticipants will receive oral Sodium Copper Chlorophyllin at a dose of 750mg once daily (OD) on an empty stomach.
Receives: Drug: Sodium Copper Chlorophyllin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline

  2. 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.

    Measured: Post 1 month

  3. 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.

    Measured: Post 3 months

  4. 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.

    Measured: Post 6 months

Secondary outcomes (4)
  1. 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.

    Measured: Baseline, post 1 month, post 3 months

  2. 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].

    Measured: Post 3 months

  3. 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.

    Measured: Baseline to up to 3 months

  4. 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.

    Measured: Baseline, post 1 month, post 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2022
  2. Study start26 Mar 2022
  3. Primary completion31 Mar 2024 (estimated)
  4. Study completion31 Mar 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A prospective, single centre, single-arm, interventional phase II study.
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05348239
Sponsor's protocol ID
900878
Acronym
CLARITY
Status last verified
Apr 2022
First submitted
17 Mar 2022
Last updated
27 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: All study-related information will be strictly maintained and will be shared only with the IEC and DSMB authorities.

Publications

  • Smit SG, Heyns CF. Management of radiation cystitis. Nat Rev Urol. 2010 Apr;7(4):206-14. doi: 10.1038/nrurol.2010.23. Epub 2010 Mar 9.

    PubMed 20212517
  • Browne C, Davis NF, Mac Craith E, Lennon GM, Mulvin DW, Quinlan DM, Mc Vey GP, Galvin DJ. A Narrative Review on the Pathophysiology and Management for Radiation Cystitis. Adv Urol. 2015;2015:346812. doi: 10.1155/2015/346812. Epub 2015 Dec 22.

    PubMed 26798335
  • Sandhu SS, Goldstraw M, Woodhouse CR. The management of haemorrhagic cystitis with sodium pentosan polysulphate. BJU Int. 2004 Oct;94(6):845-7. doi: 10.1111/j.1464-410X.2004.05044.x.

    PubMed 15476520
  • Feldmeier JJ, Hampson NB. A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach. Undersea Hyperb Med. 2002 Spring;29(1):4-30.

    PubMed 12507182
  • Oscarsson N, Muller B, Rosen A, Lodding P, Molne J, Giglio D, Hjelle KM, Vaagbo G, Hyldegaard O, Vangedal M, Salling L, Kjellberg A, Lind F, Ettala O, Arola O, Seeman-Lodding H. Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial. Lancet Oncol. 2019 Nov;20(11):1602-1614. doi: 10.1016/S1470-2045(19)30494-2. Epub 2019 Sep 16.

    PubMed 31537473
  • Villeirs L, Tailly T, Ost P, Waterloos M, Decaestecker K, Fonteyne V, Van Praet C, Lumen N. Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: Systematic review of the recent literature. Int J Urol. 2020 Feb;27(2):98-107. doi: 10.1111/iju.14130. Epub 2019 Oct 15.

    PubMed 31617263
  • Lojanapiwat B, Sripralakrit S, Soonthornphan S, Wudhikarn S. Intravesicle formalin instillation with a modified technique for controlling haemorrhage secondary to radiation cystitis. Asian J Surg. 2002 Jul;25(3):232-5. doi: 10.1016/S1015-9584(09)60181-0.

    PubMed 12376221
  • Westerman ME, Boorjian SA, Linder BJ. Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: A contemporary evaluation. Int Braz J Urol. 2016 Nov-Dec;42(6):1144-1149. doi: 10.1590/S1677-5538.IBJU.2015.0588.

    PubMed 27509371
  • Comploj E, Pycha A, Trenti E, Palermo S, Bonatti M, Krause P, Folchini DM, Pycha A. Transarterial Embolization in the Management of Intractable Haemorrhage. Urol Int. 2021;105(1-2):95-99. doi: 10.1159/000511123. Epub 2020 Oct 16.

    PubMed 33070141
  • Linder BJ, Tarrell RF, Boorjian SA. Cystectomy for refractory hemorrhagic cystitis: contemporary etiology, presentation and outcomes. J Urol. 2014 Dec;192(6):1687-92. doi: 10.1016/j.juro.2014.06.030. Epub 2014 Jun 14.

    PubMed 24936722
  • Chlorophyll and Chlorophyllin Linus Pauling Institute Oregon State University. (Micronutrient Information)

  • Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, Qian GS, Kuang SY, Gange SJ, Jacobson LP, Helzlsouer KJ, Bailey GS, Groopman JD, Kensler TW. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14601-6. doi: 10.1073/pnas.251536898. Epub 2001 Nov 27.

    PubMed 11724948
  • Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010;15(4):360-71. doi: 10.1634/theoncologist.2009-S104.

    PubMed 20413641
  • Oriya A, Takahashi K, Inanami O, Miura T, Abe Y, Kuwabara M, Kashiwakura I. Individual differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood. J Radiat Res. 2008 Mar;49(2):113-21. doi: 10.1269/jrr.07079. Epub 2007 Dec 12.

    PubMed 18075225
  • Dainiak N. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002 Jun;30(6):513-28. doi: 10.1016/s0301-472x(02)00802-0.

    PubMed 12063018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sodium Copper Chlorophyllin in people with Hemorrhagic Cystitis, run by Tata Memorial Centre at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Dr. Gagan Prakash (022 2417 ext. 7176, gagan2311@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of Objective Response Rate (ORR) as per CTCAE v5.0. (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05348239, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.

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