Clinical trial NCT04522050: Gemcitabine-based Induction Chemotherapy Combined With Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma
Official title: A Multicenter and Prospective Clinical Trial of Gemcitabine-based Induction Chemotherapy Combined With Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The initial dose of gemcitabine is 25mg/m² once a week for 6 times. The patients are divided into 9 groups (25mg/m², 50mg/m², 100mg/m², 200mg/m², 300mg/m², 350mg/m², 400mg/m², 450mg/m², 500mg/m²) with 6 patients in each group.
Primary purpose: TREATMENT

Brief summary: Researchers conduct the clinical trial (gemcitabine combined with cisplatin induction chemotherapy followed by concurrent chemoradiotherapy with gemcitabine for locally advanced nasopharyngeal carcinoma) to evaluate the safety and effectiveness of gemcitabine in patients with locally advanced nasopharyngeal carcinoma.

Detailed description: Diagnosed as locally advanced nasopharyngeal carcinoma (stage III-IV), and pathologically confirmed as a differentiated or undifferentiated non-keratinizing nasopharyngeal carcinoma, the patient is eligible to participate in the study. Patients receive gemcitabine (1000mg/m² d1,8) and cisplatin (80mg/m², d1) every 3 weeks for 2 cycles before radiotherapy. And then intensity modulated radiotherapy (IMRT) is given a total dose of GTVnx 70Gy, GTVnd 66Gy, CTV1 60Gy and CTV2 54Gy for 33 times in total, concurrently with gemcitabine. The initial dose of gemcitabine is 25mg/m² once a week for 6 times. The patients are divided into 9 groups (25mg/m², 50mg/m², 100mg/m², 200mg/m², 300mg/m², 350mg/m², 400mg/m², 450mg/m², 500mg/m²) with 6 patients in each group. Considering about 20% of the cases of dropout, withdrawal, and loss to follow-up in clinical trials, a total of 65 cases are needed in this study. The efficacy is evaluated according to the European Solid Tumor Efficacy Evaluation Standard (RECIST1.1). After induction chemotherapy, radiotherapy, and 3 months after radiotherapy, nasopharyngeal endoscopy and magnetic resonance imaging of the would be reviewed for 1 year, 2 years, and 3 years to evaluate the curative effect. The chest CT, abdominal B-ultrasound, bone scan or PETCT examinations are reviewed to exclud distant metastases. Biopsy diagnosis can be performed for patients suspected of local residual and recurrence.

Eligibility criteria: Inclusion Criteria:

* Patients with newly histologically confirmed non-keratinizing carcinoma (according to WHO histological type)
* Tumor staged as Ⅲ-Ⅳa (according to the 8th AJCC edition staging system)
* Age :18-60
* Performance status: KPS \> 70
* Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) \< 2.5×ULN, and bilirubin \< ULN
* Renal: creatinine clearance \> 60ml/min
* Adequate marrow: leucocyte count \> 4×109/L, neutrophil count \> 2×109/L, and platelet count \> 100×109/L
* Written informed consent

Exclusion Criteria:

* History of allergy to related drugs
* Prior malignancy (except adequately treated carcinoma in-situ of the cervix or basal/squamous cell carcinoma of the skin)
* History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume)
* Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes
* Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose \> 1.5×ULN), and emotional disturbance

Primary outcomes:
measure: Maximum tolerance dose(MTD)
timeFrame: 3 years
Secondary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: 3 years
measure: Tumor response rates
timeFrame: 3 years
Other outcomes:
Locations:
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Fifth Affiliated Hospital, Sun Yat-Sen University
name: siyang wang
role: PRINCIPAL_INVESTIGATOR
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