Randomized Controlled, Multicenter Phase II Clinical Research of Toripalimab (PD-1 Inhibitor) and Endostar Combined With Radiotherapy and Chemotherapy in the Treatment of High-risk Locally Advanced Nasopharyngeal Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy
- Conditions
- Nasopharyngeal Carcinoma
- Sponsor
- First Affiliated Hospital of Guangxi Medical University
- Enrollment
- 106
- Primary Endpoint
- progression-free survival, PFS
- Status
- Not yet recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is to investigate the efficacy and safety of the induction chemotherapy + concurrent chemoradiotherapy（CCRT）combined with toripalimab and endostar treatment, in comparison with the induction chemotherapy + concurrent chemoradiotherapy（CCRT）, in treating locally advanced high-risk nasopharyngeal carcinoma
Detailed Description
GP-induced chemotherapy combined with concurrent chemoradiotherapy is the standard treatment for the locally advanced nasopharyngeal carcinoma recommended by the guidelines. However, the prognosis for T4 and/or N3 nasopharyngeal carcinoma is still poor, with the 3-year PFS of about 70%. Therefore, it is of great importance to improve the prognosis of patients with locally advanced high-risk nasopharyngeal carcinoma. Immunotherapy has been an emerging treatment method for tumors in recent years. Compared with the chemotherapy, immunotherapy has less adverse reactions, and the effects could last longer, significantly improving the prognosis and patients' quality of life. Endostar, as a VEGFR inhibitor, has good safety in treating nasopharyngeal carcinoma. Related data have shown that PD-1 and Endostar exert synergistic antitumor effects in a mouse model of lung cancer. A Phase II multi-center clinical study from our center has shown that, for patients with locally advanced low-risk nasopharyngeal carcinoma, all the 3-year OS, PFS, and DMFS for the radiotherapy combined with Endostar group were superior to the concurrent chemoradiotherapy group, and the combination of radiotherapy and Endostar lead to significantly reduced adverse effects. In clinical studies concerning other solid tumors, it has also been observed that the PD-1 inhibitors combined with VEGFR inhibitors could significantly improve the efficacy, and achieve synergistic effects. Therefore, A Phase II，randomized, prospective, multicentric clinical trail was conducted to compare the efficacy and safety of induction chemotherapy and the concurrent chemoradiotherapy plus Endostar and PD-1, followed by PD-1 treatment for half a year compared with the induction chemotherapy and the concurrent chemoradiotherapy for the T4 and/or N3 nasopharyngeal carcinoma.
Investigators
min kang
professor
First Affiliated Hospital of Guangxi Medical University
Eligibility Criteria
Inclusion Criteria
- •With ECOG score 0-
- •Subjective aged 18-65 years, male or non-pregnant female.
- •Pathologically diagnosed as nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, i.e., the WHO type II or III).
- •Stage IVa (8th AJCC/UICC stage) T4 and/or N3, untreated patients with nasopharyngeal carcinoma.
- •Agreeing to provide previously stored tumor tissue samples or perform biopsy to collect tumor tissues, which were sent to the central laboratory for the PD-L1 IHC test.
- •Hematology: white blood cells ≥ 4000 /μL; neutrophils ≥ 2000 /μL; hemoglobin ≥ 9 g/dL; and platelets ≥ 100000 /μL.
- •Liver function: ALT and AST lower than the 1.5 times (1.5 × ) the upper limits of normal (ULN); and total bilirubin \< 1.5 × ULN.
- •Renal function: serum creatinine \< 1.5 × ULN.
- •Patients signing the informed consents, and willing and able to follow the study plan (visit and treatment plan), laboratory tests, and other research procedures.
- •Exclusion criteria:
Exclusion Criteria
- Not provided
Arms & Interventions
IC＋CCRT＋Toripalimab＋Endostar
Three cycles of induction chemotherapy with GP regimen (Q3W): Gem 1000 mg/m2 d1,8; DDP 80mg/m2 d1, Q3W; IMRT (6-7 weeks, 5 times each week) combined with cisplatin for 2-3 cycles (Q3W): DDP 100 mg/m2, Q3W, 2-3 cycles; IMRT: GTVnx 70-74Gy/30-33f, 5d/w, 6-7 w; Toripalimab: 240 mg, Q3W, starting on D1, for totally 12 cycles; Endostar: 7.5 mg/m2/d, continuous intravenous pumping for 10 days, Q3W, starting on D1, for totally 5 cycles.
Intervention: Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy
IC＋CCRT
Three cycles of induction chemotherapy with GP regimen (Q3W): Gem 1000 mg/m2 d1,8; DDP 80mg/m2 d1, Q3W; IMRT (6-7 weeks, 5 times each week) combined with cisplatin for 2-3 cycles (Q3W): DDP 100 mg/m2, Q3W, 2-3 cycles; IMRT: GTVnx 70-74Gy/30-33f, 5d/w, 6-7 w.
Intervention: IC＋CCRT
Outcomes
Primary Outcomes
progression-free survival, PFS
Time Frame: 3 years
calculated from the date of randomisation to the date of the documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first. distant failure, or death from any cause, whichever occurred first.
Secondary Outcomes
- Overall Survival，OS(3 years)
- Overall response rate (ORR)(3 months)
- Distant metastasis-free survival,DMFS(3 years)
- locoregional relapse-free Survival, LRFS(3 years)
- adverse events (AEs) and severe adverse events (SAE)(3 years)