Trial Title:
Nituzumab (Taixinsheng ®） A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Clinical Study on the Efficacy and Safety of Combined Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinomatreatment of Locally Advanced Nasopharyngeal Carcinoma
NCT ID:
NCT05508347
Condition:
Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Nituzumab/placebo
Description:
Test group: 3 cycles of induction chemotherapy combined with 9 times of nituzumab
targeted therapy followed by 2-3 cycles of synchronous radiotherapy and chemotherapy
combined with 7 times of nituzumab targeted therapy, a total of 16 times of nituzumab
targeted therapy, equivalent to the whole course targeted therapy.
Control group: 3 cycles of induction chemotherapy combined with 9 times of placebo
treatment followed by 2-3 cycles of concurrent chemoradiotherapy combined with 7 times of
nituzumab targeted therapy, a total of 7 times of nituzumab targeted therapy, only
targeted therapy during concurrent chemoradiotherapy
Arm group label:
Experimental group
Arm group label:
control group
Other name:
Nituzumab injection (taixinsheng)
Summary:
Nasopharyngeal carcinoma (NPC) is a head and neck tumor. Studies have shown that more
than 70% of patients are diagnosed with locally advanced nasopharyngeal carcinoma at the
time of initial diagnosis. The 3-year survival rate of locally advanced nasopharyngeal
carcinoma after chemotherapy is over 90%, but 30% of patients still have recurrence and
distant metastasis. Therefore, while improving the level of radiation therapy technology,
we should study multidisciplinary comprehensive treatment methods and put forward the
biological concept of "cure". Induction chemotherapy can effectively create better
radiotherapy conditions for locally advanced nasopharyngeal carcinoma, especially for
patients with large lesions, improve the treatment response rate, and may reduce the
local recurrence and distant metastasis rate. After the end of neoadjuvant chemotherapy,
compared with patients who only reached SD, patients who reached CR had a significant
survival benefit; Other patients had a reduced rate of distant metastasis, which aroused
our interest, although there was no obvious survival benefit. The national multicenter
phase II clinical study showed that nitumab combined with radiotherapy significantly
improved the 3-year survival rate of patients with locally advanced nasopharyngeal
carcinoma compared with radiotherapy alone. According to the previous related research
results, nitumab combined with induction chemotherapy or concurrent chemoradiotherapy has
a certain effect on nasopharyngeal carcinoma without obvious adverse reactions. However,
prospective studies on the short-term efficacy and safety of local advanced
nasopharyngeal carcinoma combined with induction chemotherapy and concurrent
chemoradiotherapy are still lacking (Taisheng ®）。
Detailed description:
In recent years, studies have found that epidermal growth factor (EGF) is related to the
proliferation of tumor cells, and a lot of evidence shows that the overexpression of
epidermal growth factor receptor (EGFR) is related to the formation of metastases and
poor prognosis. The expression rate of EGFR in nasopharyngeal carcinoma is 68%-89%.
Therefore, the EGF/EGFR system may become a new therapeutic target for the treatment of
head and neck squamous cell carcinoma, and the monoclonal antibody binding to the
receptor becomes a potentially effective anticancer biological agent. The effect of
radiotherapy to achieve the effect of inhibiting the growth of cancer cells. It is much
higher than other solid tumors and is closely related to the prognosis of patients with
nasopharyngeal carcinoma. A retrospective paired analysis by Peng et al suggested that
induction chemotherapy combined with anti-EGFR receptor therapy may be a more effective
strategy for locally advanced nasopharyngeal carcinoma following IMRT. Nimotuzumab
(Taixinsheng®) is a recombinant humanized monoclonal antibody against EGFR jointly
developed by Baitai Biopharmaceutical Co., Ltd. and Cuban Center for Molecular
Immunology, and has been listed in 19 foreign countries. Nimotuzumab is a humanized
monoclonal antibody that can competitively inhibit the binding of endogenous ligands to
EGFR, block the downstream signal transduction pathway mediated by EGFR, thereby
inhibiting tumor cell proliferation and promoting tumor cell apoptosis , inhibit
angiogenesis and increase the sensitivity of radiotherapy and chemotherapy; due to the
characteristics of humanization and high selectivity, compared with cetuximab,
nimotuzumab has fewer adverse reactions and a lower incidence of rash. At present, phase
I and II clinical studies of Nimotuzumab (Taixinsheng®) combined with radiotherapy in the
treatment of advanced nasopharyngeal carcinoma have been completed in China, and have
been approved by the SFDA. A national multicenter phase II clinical study showed that
compared with radiotherapy alone, nimotuzumab combined with radiotherapy significantly
improved the 3-year OS of patients with locally advanced nasopharyngeal carcinoma (77.61%
vs. 84.3%, P<0.05). Therefore, in April 2009, Nimotuzumab entered the Chinese version of
the NCCN Head and Neck Cancer Guidelines.
Regarding the efficacy of nimotuzumab during concurrent chemoradiotherapy, Shi Xingyuan
et al. conducted a prospective clinical trial in 2016. The control group was treated with
concurrent chemoradiotherapy (chemotherapy single-agent cisplatin), and the experimental
group was treated with concurrent chemoradiotherapy based on the treatment of the control
group. Combined with nimotuzumab, the short-term and long-term efficacy and toxic and
adverse reactions of nimotuzumab combined with cisplatin concurrent chemotherapy in the
treatment of locally advanced (III-IVB stage) nasopharyngeal carcinoma were observed. The
results showed that in the experimental group compared with the control group, the ORR
was 100% VS.91.67% (p<0.05) at 3 months after treatment, the CR rate at 3 months after
treatment was 91.7% VS.79.3% (p<0.05), and the 5-year OS was 87.5 % VS.62.5%, (P=0.036),
the incidence of adverse reactions was basically the same (P>0.05). In 2018, Wang
retrospectively analyzed 1104 patients with stage III-IVB nasopharyngeal carcinoma, all
of whom received concurrent chemoradiotherapy after induction chemotherapy, with or
without nimotuzumab. Induction chemotherapy followed by concurrent chemoradiotherapy and
nimotuzumab was effective and well tolerated in the treatment of locally advanced
nasopharyngeal carcinoma, with a 5-year OS of 94.5% vs. 85.6% in the control group (P=
0.058), PFS 87.4 % vs. 81.3% (P=0.225), and the 5-year DMFS was 95.8% vs. 83.9%
(P=0.007), respectively, indicating that concurrent chemoradiotherapy and nimotuzumab
could achieve the best survival benefit after induction chemotherapy.
In the past, studies on the application of nimotuzumab during induction chemotherapy were
carried out. In 2014, Song et al. conducted a prospective clinical study. A total of 168
patients with nasopharyngeal carcinoma (stage II-IV) received 2-3 cycles of induction
chemotherapy (IC). ) followed by concurrent chemoradiotherapy (CCRT), of which 56
patients were added with Nimotuzumab (Nimo) and were divided into three groups: A, IC +
CCRT; group B: IC (with Nimotuzumab) + CCRT; group C: IC + CCRT (Nimotuzumab added at the
same time). IC+Nimo,+CCRT VS. IC+CCRT 5-year OS were 93.0% VS. 74.8%, P=0.038,
IC+Nimo,+CCRT VS. IC+CCRT 5-year PFS rates were 89.3% VS. .72.7% (P=0.144). There were no
significant adverse reactions in the nimotuzumab treatment group. The 5-year OS and PFS
of group C were 80.4 ± 7.9% and 76.4 ± 8.5%, respectively, which were not statistically
significant compared with group A (p = 0.257 and p = 0.611, respectively). In 2019, Lu
Ying et al. conducted a multi-center clinical study, including 58 patients in the III-IVB
NPF group (Nimotuzumab combined with PF regimen induction therapy group) and 60 TPF
patients (docetaxel, cisplatin, fluorouracil regimen induction therapy group)
Chemotherapy group), after 2 cycles of induction therapy, all patients received cisplatin
concurrently with intensity-modulated radiation therapy (IMRT). The safety and short-term
efficacy of the two groups were compared. In the induction stage, the ORR NPF VS.TPF of
cervical lymph nodes and nasopharyngeal primary lesions were 70.69% VS. 0.05). Compared
with the TPF group, induction therapy in the NPF group had a more significant effect on
cervical lymph nodes (81% vs. 60% P=0.036). There was no significant difference in
efficacy evaluation (P>0.05). During induction therapy, neutropenia and gastrointestinal
reactions were significantly improved compared with TPF group (P=0.028, P=0.049). During
the concurrent chemoradiotherapy phase, compared with the TPF group, the gastrointestinal
reaction, oral mucositis and radiodermatitis in the NPF group were significantly improved
(P=0.038, P=0.041, P=0.035). It shows that for locally advanced nasopharyngeal carcinoma
receiving cisplatin concurrent IMRT, induction therapy with nimotuzumab combined with PF
regimen has better lymph node remission rate and milder adverse reactions; the patient is
resistant to subsequent concurrent chemoradiotherapy The receptivity is better, but the
long-term efficacy needs further follow-up observation.
In addition, Zhao Chong et al. conducted an open-label, multi-center, phase II clinical
trial to explore the efficacy and adverse reactions of cisplatin and 5-fluorouracil
combined with nimotuzumab in the treatment of metastatic nasopharyngeal carcinoma after
previous treatment. In this study, PF chemotherapy The objective response rate of
patients in the combined nimotuzumab treatment group was 71.4%, the disease control rate
was 85.7%, and the median progression-free survival time was 6.47 months, which was
longer than that of the PF chemotherapy group alone in the phase III study during the
same period (patients in the PF chemotherapy group). The objective response rate was 42%,
and the median progression-free survival was 5.6 months), and in patients who received
≥12 doses of nimotuzumab-targeted therapy, the objective response rate was 92.6%, and the
median progression-free survival was 92.6%. The time was 7.29 months, and the curative
effect was significantly better than that of PF chemotherapy alone or GP chemotherapy
group.
Based on the results of previous relevant studies, nimotuzumab combined with induction
chemotherapy or concurrent chemoradiotherapy has a certain curative effect on
nasopharyngeal carcinoma, and there are no significant adverse reactions. However, there
is currently a lack of prospective application research data on the short-term efficacy
and safety of nimotuzumab (Taixinsheng®) combined with induction chemotherapy and
concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal
carcinoma.
Criteria for eligibility:
Criteria:
Inclusion criteria:
1. Voluntarily participate and sign the informed consent in writing.
2. Age: 18-70 years old, gender is not limited.
3. Nasopharynx squamous cell carcinoma diagnosed by histopathology.
4. Nasopharyngeal carcinoma 2018 AJCC (Eighth Edition) staging: t2-4n2m0 (metastatic
lymph nodes have one of the following risk factors: the shortest length of the
largest lymph node is ≥ 3cm or the lymph node is liquefied and necrotic or the lymph
node envelope is invaded) or t1-4n3m0.
5. Immunohistochemistry: EGFR (+).
6. The primary tumor can be measured.
7. Kaplan score > 70.
8. Survival expectation ≥ 6 months.
9. Women in childbearing period should ensure to take effective contraception during
the study period.
10. Hemoglobin (Hgb) ≥ 90 g / L, white blood cell (WBC) ≥ 4 × 109 / L, platelet (PLT) ≥
90 × 109 /L.
11. Liver function: ALT and / or ast < 1.5 times the upper limit of normal value (ULN),
and TBIL < 1.5 times the upper limit of normal value (ULN).
Renal function: serum creatinine < 1.5 times the upper limit of normal value (ULN);
Creatinine clearance rate shall not be lower than 60ml / min.
Exclusion criteria：
1. There is evidence of distant metastasis.
2. The primary tumor or lymph node has been treated surgically (except biopsy).
3. Patients with primary focus or lymph nodes who have received radiotherapy.
4. Those who have received epidermal growth factor targeted therapy.
5. The primary lesion has received chemotherapy or immunotherapy.
6. Have had other malignant tumors (except non melanoma skin cancer or cervical
carcinoma in situ).
7. Subjects who have received other drug tests in the past 1 month.
8. > grade I peripheral neuropathy.
9. Pregnant or lactating women and women of childbearing age who refuse contraception
during the treatment observation period.
10. Those with severe allergic history or special constitution.
11. A history of severe lung or heart disease.
12. Known to be infected with HIV virus or active viral hepatitis.
13. Received live vaccine within 30 days of the planned start of study drug treatment.
14. Those who refuse or cannot sign the informed consent form.
15. Drug or alcohol addicts.
16. Persons with personality or mental illness, without or with limited capacity for
civil conduct.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sichuan Cancer Hospital
Address:
City:
Chendu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
MEI FENG, doctor
Phone:
13076000700
Email:
freda_fm@126.com
Start date:
August 15, 2022
Completion date:
September 15, 2023
Lead sponsor:
Agency:
Sichuan Cancer Hospital and Research Institute
Agency class:
Other
Source:
Sichuan Cancer Hospital and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05508347
