Clinical trial NCT05024019: Nimotuzumab Combined With Radiotherapy in High-risk Patients With HNSCC Not Suitable for Cisplatin After Surgery
Official title: A Multicenter Clinical Study of Nimotuzumab Combined With Concurrent Radiotherapy Versus Radiotherapy Alone in High-risk Patients With Head and Neck Squamous Cell Carcinoma Not Suitable for Cisplatin After Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Nimotuzumab
HNSCC
Lead sponsor: Eye & ENT Hospital of Fudan University
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, open label, multicenter, randomized controlled clinical trial. The main purpose of the study is to evaluate the efficacy and safety of nimotuzumab combined with concurrent radiotherapy versus radiotherapy alone in high-risk patients with HNSCC not suitable for cisplatin after surgery. The subjects were randomly divided into study group (nimotuzumab combined with concurrent radiotherapy) and control group (radiotherapy alone) by 1∶1 stratified random method.

Detailed description: This study is a prospective, open label, multicenter, randomized controlled clinical trial. The main purpose of the study is to evaluate the efficacy and safety of nimotuzumab combined with concurrent radiotherapy versus radiotherapy alone in high-risk patients with HNSCC not suitable for cisplatin after surgery. The subjects were randomly divided into study group and control group by 1∶1 stratified random method. The study group received nimotuzumab (200mg, weekly, for 6 weeks) combined with concurrent radiotherapy, while the control group received radiotherapy alone. The main endpoint is 2 year disease free survival (DFS) rate.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years;
2. Histology or imaging diagnosed as head and neck (oropharyngeal cancer, hypopharyngeal cancer, laryngeal cancer) squamous cell carcinoma; oropharyngeal cancer should be p16 negative (p16 positive defined as p16 ≥ 70%);
3. The radical surgery has been completed and patients were suffered from any postoperative risk factors as follows: (1) extranodal extension (ENE); (2) pT3-4; pN2-3; (3) Nerve invasion (PNI) or vascular invasion (LVI); (4) Lymph node metastasis in zone IV or zone V (oral/oropharyngeal cancer); (5) Proximal margin (\< 5mm);
4. Immunohistochemical detection indicated the EGFR expressions were positive;
5. The patients were not suitable for cisplatin chemotherapy: (1) Age\>65 years; (2) ECOG PS score\>2; (3) Renal dysfunction (creatinine clearance \<60ml/min); (4) Severe tinnitus or hearing loss (need hearing aids or hearing tests show 25 decibels threshold or above at two consecutive frequencies); (5) peripheral neuropathy severer than 1 level ; (6) Unable to accept venous hydration, such as cardiac dysfunction or other comorbidities (judged by the investigator); (7) The patient refuses cisplatin chemotherapy;
6. Imaging examination did not suggest distant metastasis;
7. Expected survival time ≥ 6 months;
8. The following criteria must be met (No transfusion of blood or blood products within 14 days prior to screening): Hb≥90g /L; ANC≥1.0×10\*9 /L; PLT≥80×10\*9 /L; white blood cell count ≥ 4×10\*9 /L; Biochemical examination need to meet the following criteria: serum total bilirubin (TBIL) ≤1.5 ULN; aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 ULN.
9. For females of reproductive age, the patients must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and be willing to use a reliable method of contraception during the trial. Male subjects should use a reliable method of contraception from the beginning of treatment until 120 days after the last medication;
10. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

Exclusion Criteria:

1. The patients received chemotherapies, PD-1 inhibitors, monoclonal antibody against EGFR, EGFR-TKI, anti-angiogenic drugs within 4 weeks before enrollment;
2. The patients participated in other interventional clinical trials within 30 days before screening;
3. There was a history of other malignant tumors within the past 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ;
4. Poorly controlled concurrent diseases (such as heart failure, diabetes, hypertension, thyroid disease, mental illness, etc.);
5. Known to be infected with HIV virus or active viral hepatitis or tuberculosis;
6. There is major surgery within 30 days before taking the trial drug for the first time or there is planned surgery;
7. Allergic to the drugs or their components used in this program;
8. Pregnancy (confirmed by blood or urine HCG test) or breastfeeding women, or subjects of childbearing age who are unwilling or unable to take effective contraceptive measures (applicable to both male and female subjects) until at least 6 months after the last trial treatment;
9. Patients who are not suitable to participate in this research according to the evaluations of researchers;
10. Those who are unwilling to participate in this study or unable to sign the informed consent form.

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: 2 year
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 2 year
measure: Local area recurrence free survival (LRRFS)
timeFrame: 2 year
measure: Distant metastasis free survival (DMFS)
timeFrame: 2 year
measure: Quality of life assessed by EORTC QLQ-H&N35
timeFrame: 2 year
measure: Incidence of treatment-emergent adverse events
timeFrame: 2 year
Other outcomes:
measure: The change of tumor related markers
timeFrame: 2 year
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
city: Shanghai
country: China
facility: Huadong Hospital Affiliated to Fudan University
city: Shanghai
country: China
facility: Shanghai General Hospital/First People's Hospital Affiliated with Shanghai Jiao Tong University
Study officials:
References: