Clinical trial NCT05039606: Clinical Study of Radiotherapy Combined With Nedaplatin Contrast and Cisplatin for the Treatment of Locally Advanced Head and Neck Squamous Carcinoma
Official title: Prospective, Multicentric, Randomized Clinical Study of Radiotherapy Combined With Nedaplatin Contrast and Cisplatin for the Treatment of Locally Advanced Head and Neck Squamous Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Carcinoma
Keywords: Local advanced head and neck squamous carcinoma
Nedaplatin
Adverse reactions
Efficacy
Lead sponsor: Guiyang Medical University
Sponsor class: OTHER
First posted: 2021-09-09
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed as a prospective, multicenter and randomized clinical study of radiotherapy combined with Nedaplatin contrast and cisplatin for local advanced head and neck squamous SCC, aiming to explore the efficacy, safety and long-term efficacy of this trial and control groups and provide some evidence for the selection of clinical treatment options.

Detailed description: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy accounting for more than 90% of head and neck tumors and over 60% of patients with mid-to late stage (-b) stage at diagnosis.For patients with moderate and advanced head and neck squamous carcinoma, concurrent chemoradiotherapy and chemotherapy is recommended for category 1 and the preferred drug is cisplatin.The application of simultaneous chemoradiotherapy can significantly improve the overall survival rate of patients with locally advanced head and neck squamous carcinoma, and effectively reduce their local recurrence rate and distant metastasis rate.However, the application of cisplatin aggravates the toxic and side reactions, such as nausea and vomiting, radioactive oral mucosal response, nephrotoxicity and ear toxicity.Although the clinical benefit of synchronous chemochemotherapy of locally advanced head and neck squamous carcinoma with cisplatin as chemotherapy is considerable, due to its obvious toxic and side reaction, some patients can not tolerate, cannot complete the whole course of treatment and quality of life, resulting in a substantial reduction in the treatment effect.Therefore, in synchronous chemoradiotherapy of locally advanced head and NSCC, there is an urgent need to find an efficient, hypotoxic, novel chemotherapeutic agent to address this problem.

Nedaplatin is the second generation platinum derivative, for cell cycle nonspecific drugs, mechanism and efficacy similar to cisplatin, anticancer spectrum, and cisplatin without drug resistance, cisplatin resistance still has a good effect, its gastrointestinal reaction and nephrotoxicity is significantly reduced, main dose-limiting toxicity, grade marrow suppression, clinical application without hydration, patients good tolerance and convenient to use, can significantly improve the quality of life of patients.A number of foreign studies have found that nedaplatin combination chemotherapy is effective in esophageal cancer, non-small cell lung cancer and cervical cancer, patients are tolerated, and the digestive tract response is significantly reduced, which helps to ensure the integrity of the course of treatment.Wang Zhennan and other studies reported that nedaplatin can improve the radiosensitivity of NPC CNE-2 cells and show dose-dependent inhibition of tumor cells.Koizumi et al also found that nedaplatin with radiotherapy could effective sensitization.In addition, the results of a phase III randomized controlled trial from the Cancer Center of Sun Yat-sen University, which showed that the overall efficiency of nedaplatin combined radiotherapy for local advanced NPC and 2-year progression-free survival rate were no less than cisplatin (88.7%vs89.7%), and compared with the cisplatin group, gastrointestinal loss, nausea, vomiting and weight loss quality score were significantly improved.

Eligibility criteria: Inclusion Criteria:

1. voluntarily participated and signed the informed consent form in writing
2. is 18-70 and gender unlimited
3. histologically proved to be squamous cell carcinoma
4. as AJCC(version 8): -A, ⅣB head and neck squamous carcinoma unable or denied surgery; \~ A, ⅣB squamous carcinoma of the head and neck with the following postoperative risk factors: positive or proximal resection, lymph node envelope invasion, nerve and vascular invasion, primary focal pT3 or T4, N2 or N3 lymph node lesions.
5. card score ≥ 70
6. survival is expected to be ≥ for 6 months
7. fertility women should guarantee contraception during entering the study
8. Hemoglobin (HGB) ≥ 100 g/L, leukocyte (WBC) ≥ 3.5 × 10\^9 / L\*(unit normal), Platelet (PLT) ≥ 100 × 10\^9 / L(unit normal), neutrophil (WBC) ≥ 1.5 × 10\^9 / L\*(unit normal)
9. liver function: 2.5 times of the upper normal limit (ULN), gluten transaminase (ASAT) \<; total bilirubin \<1.5 × ULN
10. renal function: Serum creatinine \<ULN, endogenous creatinine clearance (Ccr) ≥ 55 ml/min
11. has no severe complications such as hypertension, diabetes, coronary heart disease, and psychiatric history
12. (no history of head and neck radiotherapy or chemotherapy within 3 months)

Exclusion Criteria:

1. has a distant transfer
2. has received epidermal growth factor targeted or immunotherapy
3. has developed other malignant tumors (except for cured basal cell carcinoma or cervical carcinoma in situ)
4. pregnant women or lactating women and women of childbearing age who refuse contraception during the treatment observation period
5. has a serious history of severe allergies or abnormalities
6. refused or cannot sign an informed consent to participate in the trial
7. substance abuse or alcohol addicts

Primary outcomes:
measure: NCI CTCAE 5.0
timeFrame: 1 year
measure: RESIST1.1
timeFrame: 1year
Secondary outcomes:
measure: overall survival
timeFrame: 5 years
measure: Progression-free survival rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
Study officials:
affiliation: The Affiliated Cancer Hospital of Guizhou Medical University
name: Feng Jin, Bachelor
role: STUDY_CHAIR
References: