Clinical trial NCT03925090: Phase II Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Combined With CCRT in NPC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-04-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Progress-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Locoregional Relapse-Free Survival (LRRFS)
timeFrame: 2 years or until the date of the last follow-up visit.
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 2 years
measure: Objective Response Rate （ORR）
timeFrame: After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment
measure: Incidence rate of adverse events (AEs)
timeFrame: 2 years
measure: Correlation between the plasma EBV DNA level and PFS
timeFrame: 2 years
measure: Correlation between pre-treatment PD-L1 expression level and PFS
timeFrame: 2 years
measure: Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS
timeFrame: 2 years
measure: Change of QoL (quality of life)
timeFrame: 1 year
measure: Number of subjects with major pathologic response (MPR)
timeFrame: 21-28 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Universitty Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen University Cancer Cente
name: Overall Study Officials Mai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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