Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy for Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04447326
• Other study ID #: FirstGuangxiMU1
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2020
• Est. completion date: June 2026

Study information

• Verified date: June 2020
• Source: First Affiliated Hospital of Guangxi Medical University
• Contact: rensheng wang, Ph.D
• Phone: 86-771-5356509
• Email: 13807806008[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 106
• Est. completion date: June 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. With ECOG score 0-1.

2. Subjective aged 18-65 years, male or non-pregnant female.

3. Pathologically diagnosed as nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, i.e., the WHO type II or III).

4. Stage IVa (8th AJCC/UICC stage) T4 and/or N3, untreated patients with nasopharyngeal carcinoma.

5. 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.

6. Hematology: white blood cells = 4000 /µL; neutrophils = 2000 /µL; hemoglobin = 9 g/dL; and platelets = 100000 /µL.

7. 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.

8. Renal function: serum creatinine < 1.5 × ULN.

9. 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:

1. Patients with nasopharyngeal carcinoma with recurrence and distant metastasis.

2. Pathologically diagnosed as keratinizing squamous cell carcinoma (WHO classification type I).

3. Patients who had undergone radiotherapy or systemic chemotherapy.

4. Pregnant or breastfeeding females, or females in fertility period while with no effective contraceptive measures.

5. Positive for HIV.

6. Having suffered from other malignant tumors (except for the cured basal cell carcinoma or cervical carcinoma in situ).

7. Having been treated with inhibitors of immune regulatory points (i.e., CTLA-4, PD-1, PD-L1, etc.).

8. With complications needing long-term application of immunosuppressive drugs, or systemic or local application of corticosteroids with immunosuppressive doses of comorbidities.

9. Patients with immunodeficiency diseases, or a history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; patients suffering from vitiligo, or asthma in childhood completely relieved, with no need of any intervention after adulthood could be included; and patients with asthma requiring bronchodilators for medical intervention could not be included).

10. With excessive usage of glucocorticoids within 4 weeks.

11. Whose laboratory examination values that did not meet the relevant standards within 7 days before participating in the research.

12. Patients with markedly reduced heart, liver, lung, kidney and/or bone marrow functions.

13. With serious and uncontrolled medical diseases and infections.

14. Using other test drugs or in other clinical trials.

15. Refusing or failing to sign the informed consent to participate in the trial.

16. With other treatment contraindications.

17. With personality or mental illness, with no or limited civil capacity.

18. Positive for hepatitis B surface antigen (HBsAg), and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) = 1000 cps/mL.

19. Patients positive for the HCV antibody test could only be included in this study with the negative results from the HCV RNA polymerase chain reaction test.

20. Unable to cooperate with regular follow-up due to psychological, social, family and geographical reasons.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy
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
• IC+CCRT
IC+CCRT

Locations

Country	Name	City	State
n/a

Sponsors (11)

Lead Sponsor	Collaborator
First Affiliated Hospital of Guangxi Medical University	Af?liated Hospital of North Sichuan Medical College, Fourth Affiliated Hospital of Guangxi Medical University, Guilin Medical College, Jiangxi Provincial Cancer Hospital, LiuZhou People's Hospital, Shandong Cancer Hospital and Institute, The Affiliated Hospital Of Guizhou Medical University, Wuhan Union Hospital, China, Xiangya Hospital of Central South University, Zhejiang Cancer Hospital

References & Publications (5)

Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. — View Citation

Kang M, Wang F, Liao X, Zhou P, Wang R. Intensity-modulated radiotherapy combined with endostar has similar efficacy but weaker acute adverse reactions than IMRT combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma. Medicine (Baltimore). 2018 Jun;97(25):e11118. doi: 10.1097/MD.0000000000011118. — View Citation

Li Y, Tian Y, Jin F, Wu W, Long J, Ouyang J, Zhou Y. A phase II multicenter randomized controlled trial to compare standard chemoradiation with or without recombinant human endostatin injection (Endostar) therapy for the treatment of locally advanced nasopharyngeal carcinoma: Long-term outcomes update. Curr Probl Cancer. 2020 Feb;44(1):100492. doi: 10.1016/j.currproblcancer.2019.06.007. Epub 2019 Jul 2. — View Citation

Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27. Erratum in: J Clin Oncol. 2018 Aug 1;36(22):2360. — View Citation

Zhang S, Huang X, Zhou L, Wu G, Lin J, Yang S, Chen J, Lin S. An open-label, single-arm phase II clinical study of induction chemotherapy and sequential Nimotuzumab combined with concurrent chemoradiotherapy in N3M0 stage nasopharyngeal carcinoma. J BUON. 2018 Nov-Dec;23(6):1656-1661. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival, PFS	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.	3 years
Secondary	Overall Survival,OS	the time from random assignment to death from any cause or censored at the date of last follow-up.	3 years
Secondary	locoregional relapse-free Survival, LRFS	the time from random assignment to local or regional relapse.	3 years
Secondary	Distant metastasis-free survival,DMFS	calculated from date of randomisation to the first distant failure	3 years
Secondary	Overall response rate (ORR)	complete response (CR) + partial response (PR)	3 months
Secondary	adverse events (AEs) and severe adverse events (SAE)	graded according to NCI CTCAE 5.0	3 years