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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

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:

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.

Sites / Locations

Tata Memorial Center (TMC)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

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

NCT ID

NCT02748707

First Posted

April 20, 2016

Last Updated

April 27, 2022

Sponsor

Tata Memorial Hospital

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

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

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

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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