| CTRI Number |
CTRI/2023/07/055047 [Registered on: 11/07/2023] Trial Registered Prospectively |
| Last Modified On: |
10/07/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Radiation Therapy
Preventive |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Study of Chlorophllin for reducing chemotherapy and radiotherapy treatment side effects in head and neck cancers |
|
Scientific Title of Study
|
A Phase 2 randomized study to assess the radioprotective effect of oral chlorophyllin in acute toxicity reduction for Head Neck cancer patients receiving radiation / chemoradiation. |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 900961 |
Other |
| Version no 2.1 Dated 15 .05. 2023 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shwetabh Sinha |
| Designation |
Ass Professor and Radiation Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 1125 11th Floor Homi Bhabha Block,Department of Radiation Oncology Tata Memorial Hospital Parel
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
02224177000 |
| Fax |
|
| Email |
shwetabhsinha23@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shwetabh Sinha |
| Designation |
Ass Professor and Radiation Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 1125 11th Floor Homi Bhabha block,Department of Radition Oncology Tata Memorial Hospital Parel
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
02224177000 |
| Fax |
|
| Email |
shwetabhsinha23@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shwetabh Sinha |
| Designation |
Ass Professor and Radiation Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 1125 11th Floor Homi Bhabha block,Department of Radiation Oncology ,Tata Memorial Hospital Parel
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
02224177000 |
| Fax |
|
| Email |
shwetabhsinha23@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Centre
Dr E Borges Road,Parel Mumbai 400012,Maharashtra |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Homi Babha Building
Dr Ernest Borges Rd
Parel East
Parel Mumbai
Maharashtra 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shwetabh Sinha |
The Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) |
Room No 8 Department of Radiation Oncology Paymaster shodhika Building ACTREC Sector 22 Kharghar ,Navi Mumbai 410210
Raigarh
MAHARASHTRA |
02227405000
shwetabhsinha23@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee III |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C139||Malignant neoplasm of hypopharynx,unspecified, (2) ICD-10 Condition: C119||Malignant neoplasm of nasopharynx,unspecified, (3) ICD-10 Condition: C109||Malignant neoplasm of oropharynx,unspecified, (4) ICD-10 Condition: C148||Malignant neoplasm of overlappingsites of lip, oral cavity and pharynx, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
Patients in the standard arm will receive a placebo tablet in a similar schedule as CHL. This placebo will be
matched in physical properties to CHL and is biologically inert.
The placebo will ensure the double blinding of the trial. The placebo tablet has a similar physical appearance
including the colour (green), shape and size as compared to the experimental drug chlorophyllin. This will
ensure true blinding and help in decreasing bias during the toxicity assessment.
Due to the placebo the PI and the patient will be blinded to the arm allocation (double blinded). The
experimental drug (chlorophyllin) may or may not cause green stool discoloration in some patients and this
can also be seen with the placebo tablets. Hence, even the in independent toxicity assessors (AK, SM) will be
blinded to the arm allocation. Additionally, the assessors will ask only questions pertaining to the direct
toxicity assessment |
| Intervention |
sodium Copper Chlorophyllin |
In the intervention arm, in addition to the routine standard of care patients will be started on CHL 750 mg OD
(provided by IDRS lab, Bengaluru) 7 days prior to the planned RT start date (morning empty stomach). During
the course of RT patients will take CHL 750 mg OD 1 hour prior to planned RT delivery (at least 4 hours empty
stomach) every day. After the completion of RT patients will take CHL 750 mg OD once daily in the morning
(empty stomach) for 7 days.
The compliance to CHL will be ensured by the nursing coordinator assigned to the trial. For patients who
undergo a feeding tube insertion during RT, CHL will be given after crushing in water via the nasogastric tube.
CHL will be stopped in patients who have any severe side effects likely due to CHL.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
A.Patients with histologically proven Squamous Cell Carcinoma of the Oropharynx, Nasopharynx, Oral Cavity, Larynx and Hypopharynx planned for curative intent RT (either definitive or post-op).
B. Patients who have not received any other cancer directed treatment in the past.
C. Patients willing to sign the informed consent form. |
|
| ExclusionCriteria |
| Details |
A. Patients who have received NACT before local therapy
B. Patients > 70 years of age
C. Patients with severe comorbidities (> 2 ACE 27 score)
D. Patients with baseline feeding tube
E. Synchronous / Metachronous Primaries
F. Non-Squamous Histology
G. Patients receiving non-platinum concurrent chemotherapy
H. Treated with palliative intent
I. Not reliable for follow up |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of patient with any incidence of grade 3 or higher toxicity in 4 domains: Dermatitis, Mucositis, Dysphagia, Xerostomia) by CTCAE v 5.0 assessed during the course of RT to after 3 months post Ral Acute toxicity burden |
After 3 months of Radiation Therapy |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
A. Acute grade 2 dermatitis, Acute grade 2 mucositis Acute grade 2 dysphagia
Acute grade 2
xerostomia assessed by CTCAE version 5.0 scintigraphy.
B. Acute grade 2 hematologic toxicities.
C. Late grade 2 skin toxicity late grade 2 subcutaneous fibrosis Late grade 2 dysphagia, Late grade 2
xerostomia, Late Grade 2 Hypothyroidism.
D. EORTC QLQC 30 & HN 43 questionnaire at baseline conclusion & at all follow ups.
E. Local Control Locoregional Control, Disease free survival and Overall survival
F. Compliance to treatment
G. TAME score comparison |
at any time during the course of RT to 3 months post completion of RT |
|
|
Target Sample Size
|
Total Sample Size="220"
Sample Size from India="220"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
24/07/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Head and Neck cancers are one of the commonest cancers in India. Radiation Therapy (RT) either alone or in combination with chemotherapy (chemoradiotherapy-CTRT) is one of the common treatments of head and neck cancers with around 60-80% of patients in India. While RT/ CTRT remains a very effective treatment for head and neck cancers, there are some side effects associated with them including - skin peeling, skin discoloration, mouth ulcers, eating/ swallowing difficulty, dryness of mouth, fever and reduced blood counts. These side effects cause significant deterioration in quality of life of head and neck cancer patients. Recently a study from BARC has demonstrated the benefit of using chlorophyllin (CHL) tablets as an agent which can reduce the side effects associated with RT/ CTRT in certain cancers. This drug is well tolerated and has minimal side effects in the previous studies conducted. However, till date there is no data about the benefit of CHL in head and neck cancers In this study, patients with head and neck cancers will be randomly given Chlorophyllin tablets or a placebo (a placebo is an inactive substance that looks like the drug or treatment being tested) when they are receiving RT/ CTRT. Our primary aim is to assess if CHL can reduce the toxicity of radiotherapy/ chemoradiotherapy in head and neck cancers.
OBJECTIVES OF THE STUDY:To assess the efficacy and safety of oral CHL in reducing the acute side effects of RT/ CTRT in HNSCC
It is Phase II Prospective Randomized Placebo controlled trial.
METHODS & INTERVENTIONS
All patients will be discussed in a multidisciplinary tumor board before initiation of RT. The indications of addition of concurrent chemotherapy will be as per standard institutional and national guidelines
In the intervention arm, in addition to the routine standard of care patients will be started on CHL 750 mg OD (provided by IDRS lab, Bengaluru) 7 days prior to the planned RT start date (morning empty stomach). During the course of RT patients will take CHL 750 mg OD 1 hour prior to planned RT delivery (at least 4 hours empty stomach) every day. After the completion of RT patients will take CHL 750 mg OD once daily in the morning (empty stomach) for 7 days. The compliance to CHL will be ensured by the nursing coordinator assigned to the trial. For patients who undergo a feeding tube insertion during RT, CHL will be given after crushing in water via the nasogastric tube. CHL will be stopped in patients who have any severe side effects likely due to CHL.
Patients in the standard arm will receive a placebo tablet in a similar schedule as CHL. This placebo will be matched in physical properties to CHL and is biologically inert. The placebo will be provided by IDRS lab, Bengaluru.
The acute toxicity (primary endpoint) will be assessed at any time during the course of RT to 3 months post completion of RT. The primary hypothesis of the study is that CHL will decrease the proportion of patients with grade 3+ acute toxicity (dermatitis, mucositis, dysphagia and xerostomia) from 40% in the standard arm to 25% in the CHL arm. This corresponds to an effect size of 0.33. For an alpha=0.1 and Beta=80%, this corresponds to 100 patients in each arm accrued over 2.5 years (One sided Fisher’s exact test). Assuming a 10% attrition rate the total sample size of the study is n=220 (110 in each arm). The expected duration of trial will be 24 months.
QOL analysis will be conducted using the following tools (with appropriate language translations) ◠EORTC QLQ-30 ◠EORTC QLQ – H&N43 QOL analysis will be conducted at every patient visit & Follow Up visits as well.
|