Safety and Efficacy Study of Icotinib With Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Phase Ⅰ/Ⅱ Study of Icotinib Hydrochloride Combined With Intensity-modulated Radiotherapy in Nasopharyngeal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01534585
• Other study ID #: YHH-201201
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 13, 2012
• Last updated: April 16, 2018
• Start date: February 2012
• Est. completion date: February 2015

Study information

• Verified date: April 2018
• Source: Taizhou Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Nasopharyngeal carcinoma (NPC) is a prevalent disease in southeast of China. Radiation therapy with or without chemotherapy is a standard therapy for nasopharyngeal cancer. Cytotoxic chemotherapy plays an important role in the curative treatment of advanced NPC. However, concurrent chemoradiotherapy increased significantly local and systemic toxic effects, which may preclude many patients from proceeding with combined therapy. The epidermal growth factor receptor(EGFR) gene is amplified in 40% and EGFR protein is overexpressed in over 80% of NPC. EGFR overexpression is also associated with shorter survival following chemoradiotherapy in locoregionally advanced NPC. And some basic researches have proved that EGFR tyrosine kinase inhibitors(TKIs) could increase the radiosensitivity and reduce the epithelial-mesenchymal transition (EMT) in NPC cell line. Moreover, distant metastases has been the major cause of treatment failure in NPC. Icotinib hydrochloride is a novel oral EGFR TKIs with low mammalian toxicity(made in China). But base on toxic effects of Icotinib, it may increase toxic effects about skin and mucosa in combination therapy with Icotinib and Intensity-modulated Radiotherapy (IMRT). The prospective study will assess the tolerability and efficacy of Icotinib combined with IMRT in patients with NPC. This regimen is of great interest and it has potential to alleviate the adverse effects, improve patient compliance and better therapeutic ratio.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 2015
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with histological proof of squamous carcinoma of the nasopharynx.

2. Patients must have ECOG Performance Status of 0-1.

3. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of >/= 1500 cells/mm3, platelet count of >/= 100,000 cells/mm3; adequate hepatic function with bilirubin </= 1.5mg/dl, AST and ALT </= 2x the upper limit of normal; serum creatinine </= 1.5mg/dl, creatinine clearance >/= 50 ml/min and INR 0.8 - 1.2.

4. Patients must sign a study specific informed consent form prior to study entry.

Exclusion Criteria:

1. Evidence of metastases by clinical or radiographic examinations.

2. History of malignancy other than non-melanoma skin cancer.

3. Prior chemotherapy or anticancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region except for radioactive iodine therapy.

4. Patients with uncontrolled intercurrent disease.

5. Patients with currently active malignancy.

6. Pregnant or lactating women Female patients of childbearing potential who are unwilling to practice adequate contraception during study treatment and for two months after the last administration of study drug.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Icotinib
Oral Icotinib begins on day 1 and continues until completion of radiotherapy. Phase I:The initial plan is to accrue 6 patients to each dose level (125mg, qd and bid and tid) in each cohort. If one or none of six patients have dose limiting toxicity (DLT), then escalation will proceed. If DLT occurs in two or more patients at a dose level, then escalation will be stopped. The dose level below that at which two of six patients experience a DLT is defined as the maximum-tolerated dose. A minimum of 4 weeks of observation is required after completion of radiation within each Icotinib dose level before accrual to the next level. Phase II:According to the maximum tolerated dose, 50 patients will been recruited.

Radiation:
• intensity-modulated radiotherapy
The nasopharyngeal regions and upper neck with IMRT plans will be generated and approved for each patient, whereas the low-neck and supraclavicular regions will be used with a conventional anterior field. A total of 70-76Gy at 2.12-2.3Gy/fraction/d will be given to the GTVnx, the GTVnd will receive 66-70Gy at 2.0-2.12Gy/fraction/d, the CTV1 will receive 60-66Gy at 1.8-2.0Gy/fraction/d, and the CTV2 received 56-60Gy at 1.7-1.8Gy/fraction/d with IMRT. The low-neck and supraclavicular regions will receive 50-60Gy at 2.0Gy/fraction/d with conventional radiotherapy. Target prescription dose and critical structures limit dose are planned according to the RTOG0225 trial.

Drug:
• Paclitaxel and Cisplatin
AC that consisted of two cycles of paclitaxel 135 mg/m2 on day 1 plus cisplatin 30 mg/m2 on days 1-3 will start 4 weeks after the end of CRT.

Other:
• Quality of life
The EORTC QLQ-C30 and H&N35 of the Chinese version, which is obtained from the Quality of Life Unit, EORTC Data Center in Brussels, Belgium, is available and easily completed by our patients are chosen for this study. Patients will complete the questionnaire before treatment and after treatment and one month after treatment and three months after treatment and one year after treatment.

Genetic:
• Epidermal growth factor receptor status
EGFR expression and mutation before treatment.

Locations

Country	Name	City	State
China	Taizhou Hospital, Wenzhou Medical College	Taizhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Taizhou Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: the maximum tolerated dose of Icotinib in combination with IMRT for NPC		30 days
Primary	Phase II: 2 years locoregional control rate		Two years
Secondary	The overall response rate (complete and partial response)		1 month following treatment and then every 3 months
Secondary	The acute and late toxicity profile associated with the study regimen		1 month following treatment and then every 3 months
Secondary	The duration of control of locoregional disease		1 month following treatment and then every 3 months
Secondary	Overall survival, disease-free survival, and distant relapse rates		At time of locoregional disease progression
Secondary	EGFR status in tissue and blood before treatment		2 week of pretreatment