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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)

Primary Purpose

Oral Squamous Cell Carcinoma, Carcinoma of Buccal Mucosa, Tongue Cancers

Status
Active
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Arm1
Arm 2
Arm 3
Arm 4
Sponsored by
Tata Memorial Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. All patients with squamous cell carcinoma of oral cavity (T2-T4, N1-2, M0) and are candidates for first line curative surgical treatment and are able to swallow orally, preoperatively.
  2. Patients must be at least 18 years of age.
  3. All patients must sign an informed consent before enrolling in study.
  4. Patients must be able and willing to return to the clinic at appropriately scheduled intervals.
  5. No use of systemic steroids or topical oral steroid preparations within three months. (Topical nasal steroid sprays or cutaneous preparations with minimal systemic absorption for nasal or dermatologic disorders are allowed).
  6. Premenopausal women must be using adequate birth control methods and have a negative pregnancy test prior to entry.
  7. Karnofsky Performance Score above 80.
  8. The subject is willing and able to fully participate for the duration of the study.
  9. If applicable, the subject has been counseled on smoking cessation.
  10. The subject meets the following laboratory eligibility criteria during a time not to exceed 4 weeks prior to randomization.
  11. Hemoglobin level above 10gm/dl, the lower limit of normal.
  12. WBC count > 3,000 mm3.
  13. Platelets count > 100,000 m3.
  14. Total bilirubin, AST (Aspartate Aminotransferase) and ALT (Alanine transaminase) ≤ 2 x ULN.
  15. Serum creatinine ≤ 2 x Upper limit of Normal (ULN)

Exclusion Criteria:

1. History of cardiovascular co morbidities 2. Patients with previous history of head and neck cancers 3. Recent massive gastrointestinal hemorrhage 4. An on-going unmanaged serious infectious disease or major metabolic disorder 5. Neutrophil count of <1 x 109 per liter or platelet count of < 75 x 109 per liter at study entry, 6. Bilirubin at >1.5-fold above the upper limit of normal, and 7. Kidney failure (Glomerular filtration rate of <40 mL/min). 8. Pregnant women 9. Use other nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids within 2 weeks prior to initial clinical evaluation 10. The subject is, in the opinion of the Institutional Principal Investigator, not an appropriate candidate for study participation.

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Sites / Locations

  • Tata Memorial Center (TMC)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Sham Comparator

Arm Label

Arm 1

Arm 2

Arm 3

Arm 4

Arm Description

Celecoxib 200mg twice daily for 21 days

Erlotinib 150 mg once daily for 21 days

Celecoxib 200 mg twice daily for 21 days and Erlotinib 150 mg once daily for 21 days

Control group with no drug

Outcomes

Primary Outcome Measures

Change in expression of selected biomarkers in tissue samples, assessed by immunohistochemistry (IHC) and PCR
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.

Secondary Outcome Measures

Clinical and radiological Change in tumor size and appearance

Full Information

First Posted
April 20, 2016
Last Updated
April 27, 2022
Sponsor
Tata Memorial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02748707
Brief Title
Effect of COX-2 and EGFR Suppression on Molecular Markers of Angiogenesis and Proliferation in Squamous Cell Carcinoma of Oral Cavity - Prospective Randomized Study
Acronym
ERLO-XIB
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.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 18, 2015 (Actual)
Primary Completion Date
February 12, 2018 (Actual)
Study Completion Date
April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tata Memorial Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Squamous Cell Carcinoma, Carcinoma of Buccal Mucosa, Tongue Cancers, Head and Neck Cancers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Celecoxib 200mg twice daily for 21 days
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Erlotinib 150 mg once daily for 21 days
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
Celecoxib 200 mg twice daily for 21 days and Erlotinib 150 mg once daily for 21 days
Arm Title
Arm 4
Arm Type
Sham Comparator
Arm Description
Control group with no drug
Intervention Type
Drug
Intervention Name(s)
Arm1
Other Intervention Name(s)
Celecoxib
Intervention Description
Drug (Celecoxib as 200mg twice daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
Intervention Type
Drug
Intervention Name(s)
Arm 2
Other Intervention Name(s)
Erlotinib
Intervention Description
Drug (ERLOTINIB 150 mg daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery
Intervention Type
Drug
Intervention Name(s)
Arm 3
Other Intervention Name(s)
Celecoxib + Erlotinib
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Arm 4
Other Intervention Name(s)
Observation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in expression of selected biomarkers in tissue samples, assessed by immunohistochemistry (IHC) and PCR
Description
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.
Time Frame
baseline and 21 days
Secondary Outcome Measure Information:
Title
Clinical and radiological Change in tumor size and appearance
Time Frame
baseline and 21 days
Other Pre-specified Outcome Measures:
Title
Disease free survival
Time Frame
Date of randomization to date of disease recurrence, or appearance of a new primary or death.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients with squamous cell carcinoma of oral cavity (T2-T4, N1-2, M0) and are candidates for first line curative surgical treatment and are able to swallow orally, preoperatively. Patients must be at least 18 years of age. All patients must sign an informed consent before enrolling in study. Patients must be able and willing to return to the clinic at appropriately scheduled intervals. No use of systemic steroids or topical oral steroid preparations within three months. (Topical nasal steroid sprays or cutaneous preparations with minimal systemic absorption for nasal or dermatologic disorders are allowed). Premenopausal women must be using adequate birth control methods and have a negative pregnancy test prior to entry. Karnofsky Performance Score above 80. The subject is willing and able to fully participate for the duration of the study. If applicable, the subject has been counseled on smoking cessation. The subject meets the following laboratory eligibility criteria during a time not to exceed 4 weeks prior to randomization. Hemoglobin level above 10gm/dl, the lower limit of normal. WBC count > 3,000 mm3. Platelets count > 100,000 m3. Total bilirubin, AST (Aspartate Aminotransferase) and ALT (Alanine transaminase) ≤ 2 x ULN. Serum creatinine ≤ 2 x Upper limit of Normal (ULN) Exclusion Criteria: 1. History of cardiovascular co morbidities 2. Patients with previous history of head and neck cancers 3. Recent massive gastrointestinal hemorrhage 4. An on-going unmanaged serious infectious disease or major metabolic disorder 5. Neutrophil count of <1 x 109 per liter or platelet count of < 75 x 109 per liter at study entry, 6. Bilirubin at >1.5-fold above the upper limit of normal, and 7. Kidney failure (Glomerular filtration rate of <40 mL/min). 8. Pregnant women 9. Use other nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids within 2 weeks prior to initial clinical evaluation 10. The subject is, in the opinion of the Institutional Principal Investigator, not an appropriate candidate for study participation. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudhir V Nair, MBBS, MS,MCh
Organizational Affiliation
Tata Memorial Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tata Memorial Center (TMC)
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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