Concurrent and Adjuvant PD1 Treatment Combined With Chemo-radiotherapy for High-risk Nasopharyngeal Carcinoma

NCT04453826 | Recruiting Phase 3 DMC

• 1 other identifier: SYSUCC-MYC-2020-1103
• Study Type: interventional
• Target: 388
• Locations: 1 country
• Sites: 6

Brief Summary

Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that concurrent and adjuvant PD-1 treatment added to chemo-radiotherapy could further decrease the rate of disease progression and improve the survival outcome of high risk patients with nasopharyngeal carcinoma compared with those treated with chemo-radiotherapy alone.

Conditions

Nasopharyngeal Cancer; Chemotherapy; Radiotherapy; PD-1 Therapy

Outcome Measures

Primary Outcomes (1)

• Progress-free survival (PFS)

  Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (7)

• Overall Survival (OS)

  3 years

• Distant Metastasis-Free Survival (DMFS)

  3 years

• Locoregional Relapse-Free Survival (LRRFS)

  3 years

• Incidence of treatment related acute complications

  up to 1 years

• Incidence of treatment related late complications

  up to 3 years

Study Arms (2)

Camrelizumab plus chemo-radiotherapy arm

EXPERIMENTAL

3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy with concurrent and adjuvant camrelizumab therapy.

Drug: Camrelizumab plus chemo-radiotherapy

Chemo-radiotherapy arm

ACTIVE COMPARATOR

3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy.

Drug: Chemo-radiotherapy alone

Interventions

Camrelizumab plus chemo-radiotherapy DRUG

1. Camrelizumab: 200 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of camrelizumab are concurrently used during radiotherapy and camrelizumab are maintained for 1 year after the end of radiotherapy. 2. Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks. 3. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 4. IMRT: PTVnx#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy

Camrelizumab plus chemo-radiotherapy arm

Chemo-radiotherapy alone DRUG

1. Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks. 2. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 3. IMRT: PTVnx#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy

Chemo-radiotherapy arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Staged as T4N0-2M0,T1-4N3M0 (stage IVa) at diagnosis (according to the 8th AJCC edition).
• Staged as T1-3N1-2M0, T2-3N0M0 (stage II-III) with SD/PD according to RECIST criteria or EBV DNA of \>0 copies/mL after 3 cycles of GP induction chemotherapy.
• Aged between 18-70 years.
• Karnofsky scale (KPS)≥70.
• Normal bone marrow function.
• Normal liver and kidney function:
• total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal limit;
• creatinine clearance rate of at least 60 mL/min or creatinine of no more than 1.5 times the upper normal limit.
• Given written informed consent.

You may not qualify if:

• Histologically confirmed keratinized squamous cell carcinoma (WHO type I) or basal squamous cell carcinoma.
• Recurrent or metastatic nasopharyngeal carcinoma.
• Staged as II-III which is evaluated as PR or CR and EBV DNA of 0 copies/mL after 3 cycles of GP induction chemotherapy.
• Has known allergy to large molecule protein products or any compound of study therapy.
• Has known subjects with other malignant tumors.
• Has any active autoimmune disease or history of autoimmune disease.
• Has a history of psychiatric substance abuse, alcoholism, or drug addiction.
• The laboratory examination value does not meet the relevant standards within 7 days before enrollment
• Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study medication.
• Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year.
• Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.
• Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll.
• Has a known history of human immunodeficiency virus (HIV).
• Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive.
• Has received a live vaccine within 4 weeks of planned start of study therapy.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator
• Yuebei People's Hospital: collaborator
• Wuzhou Red Cross Hospital: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (6)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

NOT YET RECRUITING

Yuebei People's Hospital

Shaoguan, Guangdong, 512025, China

NOT YET RECRUITING

Zhongshan People's Hospital

Zhongshan, Guangdong, 528403, China

RECRUITING

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, 519000, China

RECRUITING

Wuzhou Red Cross Hospital

Wuzhou, Guangxi, 543002, China

NOT YET RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

camrelizumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Ming-Yuan Chen, MD, PhD

CONTACT

: 86-20-87343624; chmingy@mail.sysu.edu.cn

Rui You, MD, PhD

CONTACT

86-13580439820; yourui@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Doctor

Study Record Dates

• First Submitted: June 27, 2020
• First Posted: July 1, 2020
• Study Start: September 1, 2020
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 28, 2020

Record last verified: 2020-09

Locations

CN (6)