NCT02748707

Effect of COX-2 and EGFR Suppression on Molecular Markers of Angiogenesis and Proliferation in Squamous Cell Carcinoma of Oral Cavity - Prospective Randomized Study

Effect of COX-2 (Cyclooxygenase-2) and EGFR (Epidermal Growth Factor Receptor) Suppression on Molecular Markers of Angiogenesis and Proliferation in Squamous Cell Carcinoma of Oral Cavity - Prospective Randomized Study.

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Tata Memorial Hospital · Other Government
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II randomized clinical trial to study the effect of COX-2 inhibitor Celecoxib and EGFR tyrosine kinase inhibitor Erlotinib alone or in combination on molecular markers of apoptosis and angiogenesis.

Detailed description

Activation of EGFR signalling can lead to increased transcription of COX-2. Increased COX-2 transcription results in enhanced production of PGs, including PGE2, which in turn can activate EGFR initiating a positive feedback loop. Although majority of HNSCC over-express EGFR, the clinical responses to EGFR targeting agents have been modest. When the mechanisms of intrinsic resistance are identified like the mutations in the EGFR receptor, alternative therapeutic approaches should be employed. In preclinical studies, combining an inhibitor of COX-2 with an inhibitor of EGFR tyrosine kinase was more effective than either agent alone in suppressing tumor formation. Acquired resistances that may be amenable to pharmacological intervention include deregulation of EGFR degradation, constitutive activation of overlapping signal transduction pathways, especially cMET/HER3, the PI3K/Akt resistance pathway, angiogenesis and epithelial to mesenchymal transition. Preclinical data suggest that COX-2 inhibitors can affect most of the described acquired EGFR resistance pathways. We propose a prospective phase II randomized trial based on a 2 X 2 factorial design in which patients are randomized to COX-2 inhibition vs. no COX-2 inhibition. Each arm will be further randomized to erlotinib vs. no erlotinib. This results in the following treatment combinations. Arm 1: Celecoxib 200mg twice daily Arm 2: Celecoxib 200mg twice daily + Erlotinib 150mg daily Arm 3: Erlotinib 150mg alone Arm 4: Control group with no drug Patients in the drug treatment arm will receive the prescribed drug for 21 days before the tumor being surgically resected. Having a control group is ethically justifiable because the average waiting time in our hospital prior to definitive treatment is 30 days after diagnosis. The study population consists of any patients with resectable oral cavity squamous cell carcinoma seen at Tata memorial hospital. Tumor size will be estimated by MRI Scans as well as by clinical examination before and after completion of the study drugs.

Conditions

• Oral Squamous Cell Carcinoma
• Carcinoma of Buccal Mucosa
• Tongue Cancers
• Head and Neck Cancers

Interventions

Type	Name	Description
DRUG	Arm1	Drug (Celecoxib as 200mg twice daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
DRUG	Arm 2	Drug (ERLOTINIB 150 mg daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
DRUG	Arm 3	Drugs (Celecoxib 200mg twice daily and Erlotinib 150mg once daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
OTHER	Arm 4	Patients randomized to this arm will be observed for 21 days before definitive treatment by surgery.Having a control group is ethically justifiable because the average waiting time in our hospital prior to definitive treatment is 30 days after diagnosis.

Timeline

• Start date: 2015-08-18
• Primary completion: 2018-02-12
• Completion: 2023-04-01
• First posted: 2016-04-22
• Last updated: 2022-04-28

Locations

1 site across 1 country: India