| CTRI Number |
CTRI/2024/04/065397 [Registered on: 08/04/2024] Trial Registered Prospectively |
| Last Modified On: |
08/04/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Surgical/Anesthesia |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
TO CHECK THE SAFETY OF WARM CHEMOTHERAPY FOR ADVANCED ORAL CANCERS |
|
Scientific Title of Study
|
Phase I study to assess the safety of hyperthermic intracavitary chemotherapy in advanced oral cavity cancer |
| Trial Acronym |
HICOC |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Arjun Singh |
| Designation |
Assistant Professor |
| Affiliation |
TATA MEMORIAL CENTRE |
| Address |
Department of Head and Neck Oncology, Tata Memorial Centre, Dr. E Borges Marg, Parel, Mumbai 400012, India
Department of Head and Neck Oncology, Tata Memorial Centre, Dr. E Borges Marg, Parel, Mumbai 400012, India
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9743764783 |
| Fax |
|
| Email |
arjun193@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Arjun Singh |
| Designation |
Assistant Professor |
| Affiliation |
TATA MEMORIAL CENTRE |
| Address |
Department of Head and Neck Oncology, 11th Floor, Homi Bhabha Block, Dr. E Borges Marg, Parel, Mumbai 400012, India
MAHARASHTRA
400012
India |
| Phone |
9743764783 |
| Fax |
|
| Email |
arjun193@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Arjun Singh |
| Designation |
Assistant Professor |
| Affiliation |
TATA MEMORIAL CENTRE |
| Address |
Department of Head and Neck Oncology, 11th Floor, Homi Bhabha Block, Dr. E Borges Marg, Parel, Mumbai 400012, India
MAHARASHTRA
400012
India |
| Phone |
9743764783 |
| Fax |
|
| Email |
arjun193@gmail.com |
|
|
Source of Monetary or Material Support
|
| Intramural grant applied,
Department of Head and Neck Oncology, 11th Floor, Homi Bhabha Block, Dr. E Borges Marg, Parel, Mumbai 400012, India |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Centre |
| Address |
Tata Memorial Centre, Dr. E Borges Marg, Parel, Mumbai 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 |
| Arjun Singh |
Tata Memorial Centre |
Department of Head and Neck Oncology, Dr. E Borges Marg, Parel, Mumbai 400012
Mumbai
MAHARASHTRA |
9743764783
arjun193@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Tata Memorial Centre, IEC-III |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: O||Medical and Surgical, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Hyperthermic intracavitary cispaltin |
Intraoperative procedure
Once the surgery is performed, complete visual haemostasis is checked and confirmed with Valsalva maneuverer. All instruments and equipment are routinely available in the operative room at Tata Memorial Centre.
Open technique:
A flex arm retractor is attached to the operating table in a manner that will surround the cavity opening. The skin flaps will be held suspended by taking peri wound sutures using 1-0 prolene, engaging the grooves in the retractor. This will create the “well†needed to contain the agent and diluent. For the procedure, standard 14-gauge Romovac drain tubing will be used. This will continue to be used as a postoperative wound drain. The tubing will be attached to the standard tubing system used in the HIPEC procedure for the abdomen. The outflow tube (will take fluid from machine to body) having serrated holes, will be placed across the cavity starting from level V to level I (for the initial cases where only the neck will be addressed) and up to the primary site (in subsequent cases), to ensure even distribution of fluid. The input tube (will take fluid from body to machine) having serrated holes will be covered with a 2x2cm gauze piece, which act as a filter to avoid particles and other structures being drawn into the circuit via suction. This is a standard practice in the HIPEC of the abdomen. The drug will then be mixed into 0.3L/m2 normal saline (up to 600ml maximum). The water bath in the machine will be heated to 41C and maintained between 41-43C. Once adequate temperature is reached, the fluid will be circulated through the tubing. Adequate flow will be tapered so that the cavity is filled. This procedure will be performed for 60 minutes, after which the entire fluid will be drained and measured. The cavity will be washed with 1 litre of normal saline. Hemostasis and other routine checks will be performed. Adequate reconstruction will be performed for the primary tumor and the rest of the procedure is as per routine.
Closed technique:
For the procedure, standard 14-gauge Romovac drain tubing will be used. |
| Comparator Agent |
Routine surgery |
For the primary tumor, either a transoral, transmandibular, transcervical or a combination can be used. Any method chosen will be at the discretion of the investigator. Documentation of intraoperative margins is required and will be assessed by frozen section analysis if necessary. The surgeon should aim to achieve a visually-free gross margins with ≥ 5 mm microscopic margins.
The type of surgery will be at the discretion of the investigator. The initial 5 patients will include those with advanced stage disease where the primary and neck cavity can be maintained as separate cavities. Only the neck cavity will receive HICOC therapy in these patients so as to establish a protocol for the procedure. Subsequent to this, we will perform the same technique for the primary and neck simultaneously, using a barrier method for the airway in the rest of the patients.
A formal neck dissection addressing at least levels I-IV will be performed in all cases. Nomenclature will be standardized using the standard definitions of neck dissection. Resection of level V is at the discretion of the investigator. The neck dissection specimen must be oriented by the surgeon or sectioned and labelled in order to identify levels encompassed in the dissection. The surgeon will record the type of neck dissection performed (e.g. levels dissected, sparing or sacrifice of the SCM, accessory nerve, etc).
For lateralized lesions, ipsilateral neck dissection will be performed and for patients with N+ neck we recommend performing a level V clearance. Level IIb may be electively cleared based on the surgeon’s discretion as well, but we recommend its clearance in N+ classifications. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Ability to understand the procedure and willingness to sign an informed consent
2. ECOG Performance Status 2
3. Age 18 years old, up to 65 years old
4. Histopathology proven diagnosis of squamous cell carcinoma
5. Surgically resectable Stage III/IV oral cancer, as per the multidisciplinary discussion
6. Primary tumor should be lateralised so as to not require bilateral neck dissection
7. Nodal disease with/without extranodal extension on clinical examination/imaging
8. No distant metastases below the clavicles, based upon the following minimum diagnostic workup:
a. History/physical examination by the physician
b. Imaging of the head and neck (Contrast enhanced MRI for local workup and Chest CT/PET-CT for distant metastatic workup)
9. Fit for major surgery, American Society of Anesthesiologists ASA 1/2
10. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 to 2
11. Adequate organ function
12. Patients with no contraindications to Cisplatin chemotherapy and radiotherapy
13. Women of child bearing age should not be pregnant at the time of enrolment and should be willing to use adequate contraception during the treatment phase
|
|
| ExclusionCriteria |
| Details |
1. History of allergic reactions to compounds of similar chemical or biologic composition to cisplatin, carboplatin, and paclitaxel
2. Prior invasive malignancy, unless disease free for a minimum of 3 years, with the exception of radically excised basal cell
3. Prior chemotherapy for a different cancer administered within 3 years prior to registration
4. Prior radiotherapy to the region of the head and neck that would result in overlap of radiation therapy fields
5. Unresectable primary or nodal disease involving the carotid vessels, prevertebral fascia or skull base
6. Calculated GFR less 50 cc/min
7. Patients who have uncontrolled cardiac comorbidity
8. Presence of previous episode of thrombosis or embolism or presence of a prothrombotic condition in last 1 year
9. Presence of severe malnutrition
10. Severe active co-morbidities
11. Radiographic evidence of retropharyngeal and or level VI metastasis
12. Patients on other investigational drugs within last 30 days
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Dose Limiting Toxicities (DLTs) from the procedure |
At baseline; 30 days post-surgery; at 1 year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| 1. To determine patterns of locoregional failure and survival outcomes |
2 year |
| 2. To determine the compliance for treatment options |
immediate |
| 3. To determine distribution of HICOC in systemic circulation |
upto day 2 |
|
|
Target Sample Size
|
Total Sample Size="12"
Sample Size from India="12"
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 1/ Phase 2 |
|
Date of First Enrollment (India)
|
22/04/2024 |
| 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="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
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 cancer is the third most common cancer in the Indian subcontinent with oral cavity subsite being the most affected. A large number of cases report at an advanced stage (Stage III and IV). These advanced cancer patients have a higher incidence of disease returning early, even after completing the currently prescribed treatment. This has found to affect longevity and quality of life. Various treatments have been researched in an effort to prolong life in these advanced cancer patients. Moreover, with the presence of certain disease characteristics like tumours spreading into its surroundings, can affect the chances of the disease coming back again very soon. To overcome this, treatments such as chemotherapy before surgery have shown promise but can only be given up to a limited dosage via intravenous route to avoid drastic side effects. Despite this, the longevity after treatment is poor and a lot of unanswered questions remain in the treatment of these advanced cases. These issues are also present in cancers of other sites. To tackle these issues clinicians dealing with abdomen, chest and bladder cancers, a treatment involving using circulated, heated chemotherapy in the cavity has shown promising results. This is a kind of “wash†given into the cavity so that tumour cells are killed locally without any systemic side effects. In this way, the chemotherapy can be used in higher doses at the site of the cancer, without the side effects noted in the intravenous route. While this is standard practice for cancers in other places, it has not been tried in the head and neck. This study is a pilot of 12 individuals that will assess the safety and help determine a safe dose of using this method for oral cavity cancers. |