Metronomic dose finding study in patients with oral cavity cancers.

Recruitment & Eligibility

Status: ot Yet Recruiting

Sex: Not specified

Target Recruitment: 96

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.In Stage I : optimal biological effective dose (OBD) of methotrexate. <br/ ><br>2. In stage II : median PFSTimepoint: 1.In Stage I : optimal biological effective dose (OBD) of methotrexate. <br/ ><br>2. In stage II : median PFS

Secondary Outcome Measures

Name	Time	Method
1. Toxicity <br/ ><br>2. Pattern of change in biomarker <br/ ><br>3. PK-PD modellingTimepoint: 1. 3 months from start of chemotherapy <br/ ><br>2. 2 months from start of chemotherapy <br/ ><br>3. 30 hours from start of chemotherapy