Effect of COX-2 and EGFR Suppression on Molecular Markers of Angiogenesis and Proliferation in Squamous Cell Carcinoma of Oral Cavity - Prospective Randomized Study (ERLO-XIB)
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|ClinicalTrials.gov Identifier: NCT02748707|
Recruitment Status : Active, not recruiting
First Posted : April 22, 2016
Last Update Posted : April 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Oral Squamous Cell Carcinoma Carcinoma of Buccal Mucosa Tongue Cancers Head and Neck Cancers||Drug: Arm1 Drug: Arm 2 Drug: Arm 3 Other: Arm 4||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Actual Study Start Date :||August 18, 2015|
|Actual Primary Completion Date :||February 12, 2018|
|Estimated Study Completion Date :||August 2020|
Experimental: Arm 1
Celecoxib 200mg twice daily for 21 days
Drug (Celecoxib as 200mg twice daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
Other Name: Celecoxib
Experimental: Arm 2
Erlotinib 150 mg once daily for 21 days
Drug: Arm 2
Drug (ERLOTINIB 150 mg daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
Other Name: Erlotinib
Experimental: Arm 3
Celecoxib 200 mg twice daily for 21 days and Erlotinib 150 mg once daily for 21 days
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 Name: Celecoxib + Erlotinib
Sham Comparator: Arm 4
Control group with no drug
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.
Other Name: Observation
- Change in expression of selected biomarkers in tissue samples, assessed by immunohistochemistry (IHC) and PCR [ Time Frame: baseline and 21 days ]Tumor tissues will be collected and stored before and after treatment. The pre and post treatment tumor tissue will be analyzed semiquantitatively by immunohistochemistry for the levels of COX-2 (Cyclooxygenase-2), EGFR (epidermal growth factor receptor), TP53 (Tumor protein 53) and VEGF (Vascular endothelial growth factor) expression. Their baseline gene expression and fold change after treatment will be assessed by quantitative real time polymerase chain reaction (qPCR) using facility at TMC.
- Clinical and radiological Change in tumor size and appearance [ Time Frame: baseline and 21 days ]
- Disease free survival [ Time Frame: Date of randomization to date of disease recurrence, or appearance of a new primary or death. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02748707
|Tata Memorial Center (TMC)|
|Mumbai, Maharashtra, India, 400012|
|Principal Investigator:||Sudhir V Nair, MBBS, MS,MCh||Tata Memorial Center|