| CTRI Number |
CTRI/2022/09/045265 [Registered on: 06/09/2022] Trial Registered Prospectively |
| Last Modified On: |
23/09/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
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A clinical trial to study the effects of three oral drugs in low dose - Methotrexate, Cyclophosphamide and Capecitabine in patients with resectable Head and Neck cancer |
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Scientific Title of Study
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Efficacy of metronomic oral capecitabine, methotrexate and cyclophosphamide in locally advanced operable oral cavity squamous cell carcinoma - A Phase II study |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Swarnava Chanda |
| Designation |
Senior Resident |
| Affiliation |
JIPMER |
| Address |
Surgical Oncology Department, 3rd Floor, Superspeciality Block Jipmer Campus Rd, Gorimedu, Priyadarshini Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY
605006
India |
| Phone |
9026734253 |
| Fax |
|
| Email |
gameswarnava@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Prasanth Penumadu |
| Designation |
Additional Professor |
| Affiliation |
JIPMER |
| Address |
Surgical Oncology Department, 3rd Floor, Superspeciality Block Jipmer Campus Rd, Gorimedu, Priyadarshini Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY
605006
India |
| Phone |
9042092936 |
| Fax |
|
| Email |
drpenumadu@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Swarnava Chanda |
| Designation |
Senior Resident |
| Affiliation |
JIPMER |
| Address |
Surgical Oncology Department, 3rd Floor, Superspeciality Block Jipmer Campus Rd, Gorimedu, Priyadarshini Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY
605006
India |
| Phone |
9026734253 |
| Fax |
|
| Email |
gameswarnava@gmail.com |
|
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Source of Monetary or Material Support
|
|
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Primary Sponsor
|
| Name |
Swarnava Chanda |
| Address |
Jipmer Campus Rd, Gorimedu, Priyadarshini Nagar, Puducherry, 605006 |
| Type of Sponsor |
Other [Principal Investigator] |
|
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Details of Secondary Sponsor
|
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Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Swarnava Chanda |
Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) |
Surgical Oncology Department, 3rd Floor, Superspeciality Block
Jipmer Campus Rd, Gorimedu, Priyadarshini Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY |
9026734253
gameswarnava@gmail.com |
|
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Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, JIPMER |
Approved |
|
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C00||Malignant neoplasm of lip, (2) ICD-10 Condition: C02||Malignant neoplasm of other and unspecified parts of tongue, (3) ICD-10 Condition: C04||Malignant neoplasm of floor of mouth, (4) ICD-10 Condition: C03||Malignant neoplasm of gum, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
metronomic oral capecitabine, methotrexate and cyclophosphamide in locally advanced operable oral cavity squamous cell carcinoma |
Patients will be started on oral metronomic chemotherapy for 2 cycles as follows:
Each cycle will be of 28 days duration.
Methotrexate 9 mg per m2 weekly once x 4 weeks Days 1, 8, 15, 22
Capecitabine 500 mg BD continuous Days 1-28
Cyclophosphamide 50 mg OD continuous Days 1-28
|
| Comparator Agent |
Not Applicable |
Not Applicable |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
Age > 18 years
Biopsy proven Operable locally advanced oral cavity squamous cell carcinoma(T4a/4b NanyM0)
ECOG performance status 0-2
WBC count≥ 3 × 109 /L with neutrophils ≥ 1.5 × 109/L , platelet count ≥ 1 lakh/mL and Hb ≥ 9 gm/dL
Total Bilirubin ≤ 1.5 times the upper limit of normal range
AST & ALT ≤ 5 times the upper limit of normal range
Patients with measurable disease by RECIST 1.1 criteria
|
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| ExclusionCriteria |
| Details |
Inoperable oral cavity carcinoma
[Skull base invasion, prevertebral fascia involvement or carotid encasement]
Metastatic oral cavity carcinoma
Recurrent oral cavity carcinoma
|
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
|
Not Applicable |
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Blinding/Masking
|
Not Applicable |
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Primary Outcome
|
| Outcome |
TimePoints |
Among patients diagnosed with operable locally advanced oral cavity squamous cell cancer and receiving metronomic chemotherapy
To assess the clinical benefit rate
To assess the toxicity as graded by CTCAE ver 5.0
|
In every 2 weeks of therapy response will be assessed clinically as per RECIST 1.1.
Toxicity will be assessed at Day 8, Day 15, Day 28, and Day 56 of the therapy. |
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Secondary Outcome
|
| Outcome |
TimePoints |
1.To assess the 30 days post surgical morbidity as graded by Clavien Dindo classification
2.To assess the clinicopathological factors and pre-treatment VEGF gene expression with response
3.To compare the change in VEGF expression (pre-treatment and post-treatment) with response
4.To assess the two year disease free survival and overall survival and clinicopathological factors predicting survival
|
1.30 days after surgery
2.at beginning, at 8 weeks
3.at beginning, at 8 weeks
4.2 years |
|
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Target Sample Size
|
Total Sample Size="90"
Sample Size from India="90"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="90" |
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Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
15/09/2022 |
| Date of Study Completion (India) |
30/07/2024 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
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Publication Details
|
|
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
Modification(s)
|
Background Head and neck squamous cell carcinoma (HNSCC) is one of the country’s most common cancers[1]. More than half of the patients present in the advanced stage[2,3]. HNSCC can be treated with surgery and/or chemoradiotherapy in about two thirds of cases. For oral cavity cancers, the preferred modality of treatment is primary surgery. Subsequently patients receive adjuvant radiation or chemoradiation depending on the risk status. Currently, locally advanced tumor stages III and IV, local recurrences or distant metastases occur in about 40-60% of patients. Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts’ immune system, directly affecting tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing. Rationale Neoadjuvant chemotherapy has been tried in HNSCC in multiple settings, but has never been consistently shown to improve survival. In locally advanced/borderline resectable head and neck cancers, neoadjuvant chemotherapy followed by reassessment for surgery is an option as in developing countries like India due to huge patient burden all patients can not be accommodated for surgery in time and there is a long waiting period. But the usual platinum-based neoadjuvant chemotherapy is also not a standard treatment option and it has a high toxicity profile and significant mortality. It also causes nutritional depletion of patients. Novelty The effect of metronomic chemotherapy in a form of oral capecitabine, methotrexate and cyclophosphamide in a preoperative setting has not been explored earlier. Expected Outcome This study aims to evaluate the clinical response of locally advanced oral cavity cancer after administering two cycles of oral metronomic chemotherapy in a form of oral capecitabine, methotrexate and cyclophosphamide, toxicities of the oral metronomic chemotherapy schedule and also its effect on the post surgery 30 days morbidity.
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