The Effect of COX-2 Inhibitor on Radiosensitivity in Nasopharyngeal Carcinoma

• Sponsor: Changjie Huang
• Information provided by (Responsible Party): Changjie Huang, Nanning Second People's Hospital

Study Description

Brief Summary:

The purpose of this study is to determine whether celecoxib is effective in the treatment of nasopharyngeal carcinoma by concurrent chemoradiation with weekly nedaplatin.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Drug: Celecoxib; Drug: Nedaplatin; Radiation: Concurrent Radiotherapy	Phase 3

Detailed Description:

1. Study Patients:

   Patients are all recruited from the Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. All the patients provide written informed consent before enrollment. All eligible patients received a pretreatment evaluation including complete history and physical examination, endoscopic biopsy, routine laboratory tests for hematologic, renal and hepatic function as well as a dental and nutritional evaluation prior to treatment. Radiological investigations consisted of computed tomography (CT) scan or magnetic MRI of the nasopharynx, chest radiography, ultrasound of the upper abdomen and bone scintigraphy. Pathologic confirmation of nasopharyngeal cancer (NPC) was performed and re-classified according to the world health organization (WHO) subtypes.

2. Study design:

   A total of 120 NPC patients are randomly and equally divided into two groups: Nedaplatin alone concurrent radiotherapy, Celecoxib plus nedaplatin concurrent radiotherapy. The tumor response will be evaluated by magnetic resonance imaging (MRI) after 4 weeks. The tumor responses including Complete Response (CR), Partial Response (PR) , Stable Disease (SD) and Progressive Disease (PD) is defined according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. The show term or long term toxicity will be evaluated according to the National Cancer Institute Common Toxicity Criteria (NCICTC), version 3.0. All the NPC patients are requested to be followed up with an expected average of every 3 months after the therapy.The other clinical outcomes including the first evidence of cancer progression or death from any cause, the occurrence of distant metastasis, and the relapse of a local or nodal tumor will be evaluated as well. The follow-up will be up to 2018.

3. Statistical Analysis:

Statistical Package for the Social Sciences (SPSS 13.0) is used to analyze the effect of celecoxib on the nedaplatin concurrent radiotherapy. Cox's regression model and Kaplan-Meier method is used to conduct survival analysis. Clinical outcomes including the tumor responses, 1-year/3-year/5-year overall survival (OS), progression free survival (PFS), distant metastasis failure-free survival (DMFS) and locoregional failure-free survival (LFFS) will be analyzed. The multivariate Cox's regression model is used to adjust the confounders, including age and body mass index. P value less than 0.05 will be considered to be statistically significant.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	The Effect of Celecoxib on Concurrent Chemoradiation With Weekly Nedaplatin in Nasopharyngeal Carcinoma
Study Start Date :	January 2014
Estimated Primary Completion Date :	December 2016
Estimated Study Completion Date :	December 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: concurrent_radiochemotherapy; Concurrent radiotherapy with Nedaplatin 40mg/m2/week through intravenous infusion.	Drug: Nedaplatin; 40 mg/m2, IV (in the vein) on day 1 of each 7 day cycle. Number of Cycles: to the end of concurrent radiotherapy; Radiation: Concurrent Radiotherapy; The standard radiotherapy schedules were available as conventional radiotherapy and Intensity Modulated Radiotherapy (IMRT). The cumulative radiation dose was 68~74 Gy for primary tumor (2.0~2.3 Gy/f/day, 5 day/ week, /6~7 weeks), and 50~54 Gy for lymphatic positive area (1.8 ~ 2 Gy/f/day, 5 day/week, /5.0~5.5 weeks).; Other Name: standard radiotherapy schedule
Experimental: celecoxib_radiochemotherapy; Celecoxib 200mg bid po; Concurrent radiotherapy with Nedaplatin 40mg/m2/week through intravenous infusion.	Drug: Celecoxib; Celecoxib 200mg bid po, to the end of concurrent radiotherapy; Other Name: COX-2 inhibitor; Drug: Nedaplatin; 40 mg/m2, IV (in the vein) on day 1 of each 7 day cycle. Number of Cycles: to the end of concurrent radiotherapy; Radiation: Concurrent Radiotherapy; The standard radiotherapy schedules were available as conventional radiotherapy and Intensity Modulated Radiotherapy (IMRT). The cumulative radiation dose was 68~74 Gy for primary tumor (2.0~2.3 Gy/f/day, 5 day/ week, /6~7 weeks), and 50~54 Gy for lymphatic positive area (1.8 ~ 2 Gy/f/day, 5 day/week, /5.0~5.5 weeks).; Other Name: standard radiotherapy schedule

Outcome Measures

Primary Outcome Measures :

1. Number of patients with different tumor response and short term toxicity will be recorded [ Time Frame: Patients are asked to be followed within an expected average of 4 weeks after therapy ]
   The tumor responses including Complete Response (CR), Partial Response (PR) , Stable Disease (SD) and Progressive Disease (PD) were evaluated by MRI, according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0; Short term toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria (NCICTC), version 3.0.

Secondary Outcome Measures :

1. The date when each patient is dead will be recorded. [ Time Frame: Patients will be asked to be followed in an expected average of every 3 months after therapy. From date of treatment initiation until the date of first documented death from any cause, assessed up to 36 months. ]
   Overall survival (OS) is defined as the time between treatment initiation and the patient death.
2. The date when each patient shows the first evidence of cancer progression or death from any cause will be recorded. [ Time Frame: Patients will be asked to be followed in an expected average of every 3 months after therapy. From date of treatment initiation until the date of first documented progression or date of death from any cause, whichever comes first, up to 36 months ]
   Progression free survival (PFS) is defined as the time between treatment initiation and the first evidence of cancer progression or death from any cause.
3. The date when each patient presents the occurrence of distant metastasis will be recorded. [ Time Frame: Patients will be asked to be followed in an expected average of every 3 months after therapy. From date of treatment initiation until the date of first documented occurrence of distant metastasis, assessed up to 36 months ]
   Distant metastasis failure-free survival (DMFS) is defined as the time between treatment initiation and the occurrence of distant metastasis.
4. The date when each patient presents the relapse of a local or nodal tumor will be recorded. [ Time Frame: Patients will be asked to be followed in an expected average of every 3 months after therapy. From date of treatment initiation until the date of first documented relapse of a local or nodal tumor, whichever came first, assessed up to 36 months. ]
   Locoregional failure-free survival (LFFS) is defined as the time between treatment initiation and the relapse of a local or nodal tumor.
5. Long term toxicity will be recorded as the Number of Participants with Treatment-Related Adverse Events [ Time Frame: Patients will be asked to be followed in an expected average of every 3 months after therapy. From date of treatment initiation until the documented date of the Treatment-Related Adverse Events, whichever comes first, assessed up to 36 months. ]
   The Treatment-Related Adverse Events are assessed by the National Cancer Institute Common Toxicity Criteria (NCICTC), version 3.0.
6. Age will be recorded when the therapy starts [ Time Frame: Patients are asked to provide the birthday before the start of therapy ]
   Age is defined as the time between the birthday and treatment initiation.
7. Height in meters and weight in kilograms will be recorded when therapy starts [ Time Frame: Patients are asked to be measured the height and weight before the start of therapy ]
   High and weight are measured in standing posture without shoes by trained nurses. Body mass index is calculated form weight in kilograms divided by height in meters squared.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

• Patients with NPC newly diagnosed by histopathology, and without radiotherapy or chemotherapy before the clinical trial
• Patients with measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• With the Eastern Cooperative Oncology Group Performance Status (ECOG PS) as 0-1 score
• Serum hemoglobin ≥10gm/dL, platelet ≥100000/μL, neutrophil granulocyte absolute counting is 1500/μL
• Serum creatinine ≤1.25 times of upper normal limit (UNL), creatinine clearance rate ≥ 60 ml/min
• Serum bilirubin ≤ 1.5times of UNL, serum aspartate aminotransferase (AST) or glutamic-oxaloacetic transaminase(GOT)≤ 2.5 times of UNL, serum alanine aminotransferase (ALT) or glutamic-pyruvic transaminase (GPT) ≤ 2.5 times of UNL, alkaline phosphatase≤5 times of UNL
• The estimate overall survival (OS)> 6 months
• With formal informed consent forms signed.

Exclusion criteria:

• With symptomatic brain/bone metastases,
• With cognitive impairment or other malignancies
• With any contraindications for radiotherapy and chemotherapy (such as active phase of infection, myocardial infarction within 6 months, symptomatic heart disease, including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmias, in current immunosuppressive therapy)
• Current pregnancy, lactating women or women with fertility but don't take contraceptive measures yet
• With severe bone marrow dysfunction
• With bleeding tendency
• With abuse of drugs or alcohol addicts
• Who may have III-IV type of allergic reactions to any treatment in this study
• With termination of trial because of intolerable toxicity, other study drugs using during the clinical study, or unwilling to continue the treatment.

Contacts and Locations

Contacts

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Contact: Yan Mao, M.D.	+8614795721791	zijujuan@163.com

Locations

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China, Guangxi
The third Affiliated Hospital of Guangxi Medical University	Recruiting
Nanning, Guangxi, China, 530021
Contact: Yan Mao, M.D. +8614795721791 zijujuan@163.com

Sponsors and Collaborators

Changjie Huang

Investigators

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Principal Investigator:	Changjie Huang	The third Affiliated Hospital of Guangxi Medical University

More Information

Publications:

Soo RA, Wu J, Aggarwal A, Tao Q, Hsieh W, Putti T, Tan KB, Low JS, Lai YF, Mow B, Hsu S, Loh KS, Tan L, Tan P, Goh BC. Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression. Ann Oncol. 2006 Nov;17(11):1625-30. Epub 2006 Sep 28. Erratum in: Ann Oncol. 2007 Mar;18(3):611. Soon, W L [corrected to Low, J S W].

Mohammadianpanah M, Razmjou-Ghalaei S, Shafizad A, Ashouri-Taziani Y, Khademi B, Ahmadloo N, Ansari M, Omidvari S, Mosalaei A, Mosleh-Shirazi MA. Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial. J Cancer Res Ther. 2011 Oct-Dec;7(4):442-7. doi: 10.4103/0973-1482.92013.

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Responsible Party:	Changjie Huang, head of the medical department, Nanning Second People's Hospital
ClinicalTrials.gov Identifier:	NCT02537925 History of Changes
Other Study ID Numbers:	NaningSPH_2014
First Posted:	September 2, 2015
Last Update Posted:	September 2, 2015
Last Verified:	August 2015

Keywords provided by Changjie Huang, Nanning Second People's Hospital:

COX-2 inhibitors; radiosensitivity; nasopharyngeal carcinoma

Additional relevant MeSH terms:

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Carcinoma; Nasopharyngeal Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Celecoxib	Cyclooxygenase 2 Inhibitors; Nedaplatin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents