| CTRI Number |
CTRI/2018/10/015958 [Registered on: 09/10/2018] Trial Registered Prospectively |
| Last Modified On: |
08/11/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Docetaxel verses Cisplatin in Head and Neck cancer. |
|
Scientific Title of Study
|
Docetaxel or Cisplatin radiosensitizer in Head and Neck cancer patients for curative or adjuvant chemoradiation |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Kumar Prabhash |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
OPD 203/204 HBB
Tata Memorial Hospital
Parel,Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9167760576 |
| Fax |
02224146937 |
| Email |
kprabhash1@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Kumar Prabhash |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
OPD 203/204 HBB
Tata Memorial Hospital
Parel,Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9167760576 |
| Fax |
02224146937 |
| Email |
kprabhash1@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Arti Bhelekar |
| Designation |
Clinical Trial Coordinator |
| Affiliation |
Tata Memorial Hospital |
| Address |
OPD 203/204 HBB
Tata Memorial Hospital
Parel,Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9702629806 |
| Fax |
02224146937 |
| Email |
artitmh@gmail.com |
|
|
Source of Monetary or Material Support
|
| TATA MEMORIAL HOSPITAL,
Dr E Borges Road, Parel Mumbai-400012 |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Centre |
| Address |
TATA MEMORIAL CENTRE,
DR. E BORGES ROAD, PAREL MUMBAI 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shikha Goyal |
Postgraduate Institute of Medical Education and Research |
Department of radiotherapy and oncology, Room 54, Ground floor,Nehru Hospital extension Madhya Marg, Sector 12, Chandigarh, 160012
Chandigarh
CHANDIGARH |
8826136224
drshikhagoyal@gmail.com |
| Dr Kumar Prabhash |
Tata Memorial Hospital |
2nd Floor HBB,
OPD 203/204 Head Neck Medical Oncology, TMH Parel
Mumbai
MAHARASHTRA |
9224182898
kprabhash1@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institutional Ethics Comittee |
Approved |
| Institutional Ethics Comittee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C049||Malignant neoplasm of floor of mouth, unspecified, (2) ICD-10 Condition: C029||Malignant neoplasm of tongue, unspecified, (3) ICD-10 Condition: C039||Malignant neoplasm of gum, unspecified, (4) ICD-10 Condition: C059||Malignant neoplasm of palate, unspecified, (5) ICD-10 Condition: C069||Malignant neoplasm of mouth, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Cisplatin based CTRT. |
Patients in arm A would be planned for Cisplatin based CTRT. Both conventional or altered fractionation are permitted
Radical RT: For 2DRT: Phase1: 40-46 Gy/20-23 fractions, 2Gy/#, one fraction per day Phase 2: 24-30 Gy/12-15 fractions, 2Gy/#, one fraction per day Total dose to be 70 Gy/ 35 fractions/ 7 weeks Adjuvant RT: For 2DRT: Phase 1: 46 Gy/23 fractions, 2Gy/#, one fraction per day Phase 2: 14 Gy/ 7 fractions, 2Gy/#, one fraction per day Total dose to be 60 Gy/ 30 fractions/ 6 weeks For IMRT: Prescription dose should follow the ICRU 50 report. PTV1:A total dose of 44-46 Gy in 22-23 fractions over a total 5.5 weeks (Equivalent: 2 Gy/fraction, 5 fractions per week) PTV2: A total dose of 60 Gy in 30 fractions over a total 6 weeks (2 Gy/fraction, 5 fractions per week)
Chemotherapy
3 Weekly Cisplatin (100 mg/m2) with high antiemetic prophylaxis . |
| Intervention |
Docetaxel based CTRT |
Patients in arm B would be planned for Docetaxel based CTRT. Both conventional or altered fractionation are permitted.
Radical RT:
For 2DRT:
Phase1: 40-46 Gy/20-23 fractions, 2Gy/#, one fraction per day
Phase 2: 24-30 Gy/12-15 fractions, 2Gy/#, one fraction per day
Total dose to be 70 Gy/ 35 fractions/ 7 weeks
Adjuvant RT:
For 2DRT:
Phase 1: 46 Gy/23 fractions, 2Gy/#, one fraction per day
Phase 2: 14 Gy/ 7 fractions, 2Gy/#, one fraction per day
Total dose to be 60 Gy/ 30 fractions/ 6 weeks
For IMRT:
Prescription dose should follow the ICRU 50 report. PTV1:A total dose of 44-46 Gy in 22-23 fractions over a total 5.5 weeks (Equivalent: 2 Gy/fraction, 5 fractions per week) PTV2: A total dose of 60 Gy in 30 fractions over a total 6 weeks (2 Gy/fraction, 5 fractions per week)
Chemotherapy: Weekly docetaxel (15 mg/m2) with low antiemetic prophylaxis |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
85.00 Year(s) |
| Gender |
Both |
| Details |
1.Participants must have a histologically confirmed stage III-IV squamous cell cancers of the head and neck region ( AJCC-UICC staging ,8th edition).
2.Participants must warrant CTRT must warrant at least one of the following
a.Radical setting : Stage III-IV head and neck cancer
b.Adjuvant setting : Stage III-IV head and neck cancer postoperative with one of the below mentioned feature on pathology specimen
i.Extracapsular extension
ii.Margin positive
iii.Close margin ( cut margin 0.5 mm or below)
3.Participants must have malignancy arising from one of the following sites oral cavity, pharynx ( inclusive of oropharynx, hypopharynx) or larynx ( inclusive of supraglottis, glottis and subglottis) or CUP ( carcinoma unknown primary) with neck nodes
4.ECOG performance status ≤2
5.Participants must have normal organ and marrow function as defined below:
a.Leukocytes ≥3,000/mcL
b.Platelets ≥100,000/mcL
c.Total bilirubin < 1.5 × institutional upper limit of normal
d.AST(SGOT)/ALT(SGPT) ≤1.5 × institutional upper limit of normal
e.Calculated Creatinine clearance > 50 ml/min
|
|
| ExclusionCriteria |
| Details |
1.Participants who are receiving any other investigational agents.
2.Primary sites of malignancy major salivary gland or nasopharynx or skin
3.Patients with QTc prolongation defined as QTc interval greater than 480 ms in view of risk of sudden cardiac death associated with use of antiemetics.
4.History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in study.
5.Uncontrolled intercurrent illness including, but not limited to tuberculosis, diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, renal failure (on dialysis), active gastrointestinal bleeding, cerebrovascular accidents, inflammatory bowel disease, known hyperkalemia ( CTCAE version 4.02 grade 3 or above which is persistent over 1 week) or psychiatric illness/social situations that would limit compliance with study requirements.
6. Presence of grade 3 or above sensory hearing loss
7.Pregnant women and breastfeeding women are excluded from this study because docetaxel has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants. These potential risks may also apply to other agents used in this study.
8.HIV-positive, Active Hepatitis B and Active Hepatitis C seropositive patients are excluded from this study.
|
|
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Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
An Open list of random numbers |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
To compare 2 year OS between docetaxel based CTRT (D-CTRT) and cisplatin based
CTRT(C-CTRT) Secondary objectives a. To compare 2 year PFS between docetaxel based CTRT (D-CTRT) and
cisplatin based CTRT(C-CTRT) b. To compare acute and late toxicity between docetaxel based CTRT (D-CTRT)
and cisplatin based CTRT(C-CTRT) |
To compare 2 year OS between docetaxel based CTRT (D-CTRT) and cisplatin based
CTRT(C-CTRT) Secondary objectives a. To compare 2 year PFS between docetaxel based CTRT (D-CTRT) and
cisplatin based CTRT(C-CTRT) b. To compare acute and late toxicity between docetaxel based CTRT (D-CTRT)
and cisplatin based CTRT(C-CTRT) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
a. To compare 2 year PFS between docetaxel based CTRT (D-CTRT) and cisplatin based CTRT(C-CTRT)
b. To compare acute and late toxicity between docetaxel based CTRT (D-CTRT) and cisplatin based CTRT(C-CTRT) |
2years |
|
|
Target Sample Size
|
Total Sample Size="600"
Sample Size from India="600"
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 3 |
|
Date of First Enrollment (India)
|
15/10/2018 |
| 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="6"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Importance of CTRT in head and neck cancers Locally advanced head and neck cancers have poor survivals. The 2 year , 5 year and 10 year overall survival post standard fractionation radiation are 45.6%, 29.3% and 18.3% respectively ( Beitler et al, RTOG 9003).1 The addition of concurrent chemotherapy to radiation leads to an improvement in survival. The 2 year and 5 year overall survival post concurrent chemoradiation are 55 % and 33.7 % in accordance with the MACH-NC analysis .2 The benefit of the addition of chemotherapy is consistent in all tumour locations, with hazard ratios between 0.87 and 0.88 .The benefit of chemotherapy on survival does not differ significantly postoperative radiotherapy (HR 0.79 [0.68–0.91]), or curative radiotherapy with conventional (HR 0.83 [0.78–0.88]) or altered fractionation (HR 0.73 [0.65–0.82]). In accordance with MACHNC analysis there is no significant difference (p = 0.19) between mono-chemotherapy (HR 0.84) and polychemotherapy (HR 0.78). Among mono-chemotherapy group the impact of platinum was significantly higher than non platinum(p = 0.006). The hazard ratio for mono platinum was 0.74 [0.67;0.82] while it was 0.89 [0.82;0.96] for mono-non platinum therapy 2. Among platinum cisplatin HR of 5-year OS was 0.67 (95% CI, 0.49 to 0.92; P=0.01) , which showed a significant difference in favor of the cisplatin group.3 So cisplatin based chemoradiation is routinely used. In a study reported from TMH by Sarbani et al cisplatin based CTRT was associated with similar benefit. The locoregional control was better in the CTRT arm compared with the other 2 arms of Rt and accelerated RT (5 year locoregional control: RT group 32%, CTRT group 49%, and accelerated RT group 27%; p = .049; log-rank test). On comparison among the groups, the CTRT arm was significantly better than accelerated RT in terms of locoregional control (p = .01). The CRT arm showed a significantly better DFS compared with the other 2 arms (5-year DFS: RT group 25%, CRT group 39%, and accelerated RT group 20%; p = .03 |