Randomized, Placebo-controlled, Double-blind Phase II Clinical Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Immunotherapy Combined With Concurrent Chemoradiotherapy for High-risk Nasopharyngeal Carcinoma

Phase II Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Combined With CCRT in NPC Patients

Sponsors

Lead sponsor: Sun Yat-sen University

Source Sun Yat-sen University
Brief Summary

This is a randomized Phase II trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with concurrent cisplatin chemoradiotherapy versus cisplatin concurrent chemoradiotherapy plus placebo in treating patients with high risk locoregionally advanced nasopharyngeal carcinoma.

Detailed Description

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. For locoregionally advanced NPC, especially for the high risk NPC (plasma EBV DNA ≥ 1500 copies/ml), the incidence of treatment failure is still high. Although concurrent chemoradiotherapy (CCRT) can improve the treatment outcomes of these patients, approximately 25% of locoregionally advanced NPCs still develop relapse and metastasis.

Hence, there is an urgent need for novel therapies to improve survival and reduce treatment-related toxicity in NPC patients. Accumulating evidence shows that PD-1 antibody is effective for treating recurrent/metastastic NPC patients. This is a Phase II randomized trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with CCRT versus CCRT plus placebo in treating patients with high risk NPC (Stage III-IVa, AJCC 8th and EBV DNA ≥ 1500 copies/ml).

Overall Status Recruiting
Start Date December 8, 2019
Completion Date October 2023
Primary Completion Date October 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Progress-free survival (PFS) 2 years
Secondary Outcome
Measure Time Frame
Overall Survival (OS) 2 years
Locoregional Relapse-Free Survival (LRRFS) 2 years or until the date of the last follow-up visit.
Distant Metastasis-Free Survival (DMFS) 2 years
Objective Response Rate (ORR) After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment
Incidence rate of adverse events (AEs) 2 years
Correlation between the plasma EBV DNA level and PFS 2 years
Correlation between pre-treatment PD-L1 expression level and PFS 2 years
Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS 2 years
Change of QoL (quality of life) 1 year
Number of subjects with major pathologic response (MPR) 21-28 days
Enrollment 138
Condition
Intervention

Intervention type: Drug

Intervention name: Cisplatin+Toripalimab

Description: chemotherapy and monoclonal antibody

Arm group label: Neoadjuvant and Adjuvant Toripalimab+CCRT

Other name: DDP+ JS001

Intervention type: Drug

Intervention name: Cisplatin+placebo

Description: chemotherapy

Arm group label: Neoadjuvant and Adjuvant Placebo+CCRT

Other name: DDP

Eligibility

Criteria:

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III Original clinical staged as III-IVa (according to the 8th AJCC edition)

2. No evidence of distant metastasis (M0)

3. Plasm EB Virus DNA≥1500copies/ml

4. Male and no pregnant female

5. Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1

6. WBC ≥ 4×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L

7. With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 2.0×ULN)

8. With normal renal function test ( creatinine clearance ≥60 ml/min)

Exclusion Criteria:

1. Patients have evidence of relapse or distant metastasis

2. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)

3. Receiving radiotherapy or chemotherapy previously

4. The presence of uncontrolled life-threatening illness

5. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

6. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.

7. Patients who have been treated with inhibitors of immune regulation (CTLA-4, PD-1, PD-L1, etc.).

8. Patients with immunodeficiency disease and history of organ transplantation.

9. Patients who have used large doses of glucocorticoids, anti-cancer monoclonal antibodies, and other immunosuppressive agents within 4 weeks.

10. HIV positive.

11. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.

12. Severe, uncontrolled medical conditions and infections.

13. At the same time using other test drugs or in other clinical trials.

14. Refusal or inability to sign informed consent to participate in the trial.

15. Other treatment contraindications.

16. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.

17. Hepatitis B surface antigen (HBsAg) positive and HBVDNA ≥1000cps/ml.

18. Patients with positive HCV antibody test results can only be included in the study when the polymerase chain reaction of HCV RNA is negative.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Overall Study Officials Mai, MD,PhD Principal Investigator Sun Yat-Sen University Cancer Cente
Overall Contact

Last name: Qiuyan Chen, MD,PhD

Phone: 86-20-87343380

Email: [email protected]

Location
facility status contact investigator Sun Yat-sen Universitty Cancer Center Hai-Qiang Mai, MD,PhD +862087343643 [email protected] Hai-Qiang Mai, MD,PhD Principal Investigator
Location Countries

China

Verification Date

April 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Sun Yat-sen University

Investigator full name: Hai-Qiang Mai,MD,PhD

Investigator title: Deputy Director of the Department of Nasopharyngeal Carcinoma

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Neoadjuvant and Adjuvant Toripalimab+CCRT

Arm group type: Experimental

Description: Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: Toripalimab Toripalimab 240mg every 2 weeks with a total of 2 cycles as neoadjuvant anti-PD-1 immunotherapy; Toripalimab240mg every 3 weeks with a total of 8 cycles as adjuvant anti-PD-1 immunotherapy 2 weeks after CCRT Other Names:anti-PD-1 antibody, JS001

Arm group label: Neoadjuvant and Adjuvant Placebo+CCRT

Arm group type: Placebo Comparator

Description: Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: placebo placebo 240mg every 2 weeks with a total of 2 cycles as neoadjuvant treatment; placebo 240mg every 3 weeks with a total of 8 cycles as adjuvant treatment 2 weeks after CCRT.

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov