Metronomic dose finding study in patients with oral cavity cancers.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2016/04/006834
• Date of registration: 19-04-2016
• Prospective Registration: Yes
• Primary sponsor: Tata Memorial Hospital
• Public title: Metronomic dose finding study in patients with oral cavity cancers.
• Scientific title: â??Stage I/II study of oral metronomic methotrexate with celecoxib and erlotinib as palliative chemotherapy in oral cancer patientsâ??
• Date of first enrolment: 02-05-2016
• Target sample size: 96
• Recruitment status: Not Yet Recruiting
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=14050
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 1/ Phase 2

Countries of recruitment

India

Contacts

• Name: DR VIJAY PATIL
• Affiliation: TATA MEMORIAL HOSPITAL

• Name: BHAVESH P BANDEKAR
• Affiliation: TATA MEMORIAL HOSPITAL

Key inclusion & exclusion criteria

Inclusion criteria: 1.Histologically proven squamous cell cancers of oral cavity with at least one measurable lesion.

2.Age > 18 years

3.ECOG PS 0 - 2

4.No uncontrolled comorbidities

5.Not affording cetuximab based chemotherapy


Exclusion criteria: 1.Participants who are receiving any other investigational agents.

2.Patients with history of aspiration pneumonia or who are unable to swallow tablets

3.Primary sites of malignancy in major salivary gland or nasopharynx or skin

4.Patients receiving methotrexate for other indications not limited to rheumatoid arthritis

5.Patients who had received long term Cox-2 inhibitors ( more than 3 month continuous usage) will be excluded

6.Patients with hypercalcemia at presentation (defined as a corrected serum calcium of > 10.5 mg/dL).

7.Patients with QTc prolongation defined as QTc interval greater than 440 ms in males and 480 ms in females in view of risk of sudden cardiac death associated with use of celecoxib.

8.History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in study.

9.Uncontrolled intercurrent illness including, but not limited to, hypertension, 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.

10.Pregnant women and breastfeeding women are excluded from this study because celecoxib / erlotinib and methotrexate are agents with 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.

11.HIV-positive, Hepatitis B and C seropositive patients are excluded from this study.

12.Patients with previous history of other cancers.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Squamous cell cancers of head and neck region warranting palliative chemotherapy

Intervention(s)

Intervention1: Chemotherapy will be administered with tablet erlotinib 150 mg ( fixed dose ) PO OD daily, capsule celecoxib 200 mg ( fixed dose ) PO BD daily and oral weekly methotrexate.: In stage 1 : The dose of methotrexate will be according to the dose level
In stage 2 : The dose of methotrexate will be the dose selected from stage 1
Weekly oral chemotherapy with:
De escalating dose of oral methotrexate given weekly D1
1. Dose Level 0: 15 mg/m2
2. Dose Level I: 12 mg/m2
3. Dose Level II: 09 mg/m2
4. Dose Level III: 06 mg/m2
5. Dose Level IV: 03 mg/m2
Fixed dose of erlotinib 150 mg OD
Fixed dose of celecoxib 200 mg BD

Control Intervention1: Not applicable: Since there is only one arm

Primary Outcome(s)

1.In Stage I : optimal biological effective dose (OBD) of methotrexate.

2. In stage II : median PFSTimepoint: 1.In Stage I : optimal biological effective dose (OBD) of methotrexate.

2. In stage II : median PFS

Secondary Outcome(s)

1. Toxicity

2. Pattern of change in biomarker

3. PK-PD modellingTimepoint: 1. 3 months from start of chemotherapy

2. 2 months from start of chemotherapy

3. 30 hours from start of chemotherapy

Secondary ID(s)

190

Source(s) of Monetary Support

TATA MEMORIAL HOSPITAL

Secondary Sponsor(s)

NOT APPLICABLE

Ethics review

Status: Approved
Approval date: 18/01/2016
Contact:

ACTREC INSTITUTIONAL ETHICS COMMITTEE