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

Primary Purpose

Nasopharyngeal Cancer, Chemotherapy, Radiotherapy

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Camrelizumab plus chemo-radiotherapy

Chemo-radiotherapy alone

About this trial

This is an interventional treatment trial for Nasopharyngeal Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
1. total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal limit;
2. 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.

Exclusion Criteria:

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.
Pregnancy or breast feeding.

Sites / Locations

Sun Yat-sen University Cancer CenterRecruiting
Cancer Center of Guangzhou Medical University
Yuebei People's Hospital
Zhongshan People's HospitalRecruiting
The Fifth Affiliated Hospital of Sun Yat-sen UniversityRecruiting
Wuzhou Red Cross Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Camrelizumab plus chemo-radiotherapy arm

Chemo-radiotherapy arm

Arm Description

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

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

Outcomes

Primary Outcome Measures

Progress-free survival (PFS)

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

Secondary Outcome Measures

Overall Survival (OS)

Defined as the time interval from randomization to death due to any cause.

Distant Metastasis-Free Survival (DMFS)

Defined as the time interval from randomisation to the date of first distant metastases.

Locoregional Relapse-Free Survival (LRRFS)

Defined as the time from randomisation to the date of first locoregional relapse.

Incidence of treatment related acute complications

The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.

Incidence of treatment related late complications

The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment.

Full Information

NCT ID

NCT04453826

First Posted

June 27, 2020

Last Updated

September 24, 2020

Sponsor

Sun Yat-sen University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04453826

Brief Title

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

Official Title

A Multicenter Randomized Clinical Phase 3 Trial of Induction Chemotherapy Plus Concurrent Chemo-radiotherapy With or Without Camrelizumab for High Risk Nasopharyngeal Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2020 (Actual)

Primary Completion Date

September 2026 (Anticipated)

Study Completion Date

September 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Through multicenter, open-label, randomised clinical trials, high risk patients with nasopharyngeal carcinoma (staged as II-III with SD/PD according to RECIST criteria or EBV DNA of >0 copies/mL after 3 cycles of GP induction chemotherapy and staged as IVa) are randomized into camrelizumab plus chemo-radiotherapy arm and chemo-radiotherapy arm. The efficacy and safety of patients between these two arms are compared.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasopharyngeal Cancer, Chemotherapy, Radiotherapy, PD-1 Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

388 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Camrelizumab plus chemo-radiotherapy arm

Arm Type

Experimental

Arm Description

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

Arm Title

Chemo-radiotherapy arm

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Camrelizumab plus chemo-radiotherapy

Intervention Description

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. 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. 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. IMRT: PTVnx#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy

Intervention Type

Drug

Intervention Name(s)

Chemo-radiotherapy alone

Intervention Description

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. 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. IMRT: PTVnx#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy

Primary Outcome Measure Information:

Title

Progress-free survival (PFS)

Description

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

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Defined as the time interval from randomization to death due to any cause.

Time Frame

3 years

Title

Distant Metastasis-Free Survival (DMFS)

Description

Defined as the time interval from randomisation to the date of first distant metastases.

Time Frame

3 years

Title

Locoregional Relapse-Free Survival (LRRFS)

Description

Defined as the time from randomisation to the date of first locoregional relapse.

Time Frame

3 years

Title

Incidence of treatment related acute complications

Description

The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.

Time Frame

up to 1 years

Title

Incidence of treatment related late complications

Description

The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.

Time Frame

up to 3 years

Title

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)

Description

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.

Time Frame

up to 3 years

Title

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)

Description

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment.

Time Frame

up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. Pregnancy or breast feeding.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ming-Yuan Chen, MD, PhD

Phone

: 86-20-87343624

chmingy@mail.sysu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Rui You, MD, PhD

Phone

86-13580439820

yourui@sysucc.org.cn

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ming-Yuan Chen, MD, PhD

Phone

86-20-8734-3361

chmingy@mail.sysu.edu.cn

First Name & Middle Initial & Last Name & Degree

Ming-Yuan Chen, MD, PhD

Facility Name

Cancer Center of Guangzhou Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510095

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dong-Ping Chen, MD

Phone

86-13302215492

chen_dpgz@163.com

First Name & Middle Initial & Last Name & Degree

Dong-Ping Chen, MD

Facility Name

Yuebei People's Hospital

City

Shaoguan

State/Province

Guangdong

ZIP/Postal Code

512025

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Su-Ming Pan, MD

Phone

86-13826331948

First Name & Middle Initial & Last Name & Degree

Su-Ming Pan, MD

Facility Name

Zhongshan People's Hospital

City

Zhongshan

State/Province

Guangdong

ZIP/Postal Code

528403

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Feng Lei, MD

13528227676@163.com

First Name & Middle Initial & Last Name & Degree

Feng Lei, MD

Facility Name

The Fifth Affiliated Hospital of Sun Yat-sen University

City

Zhuhai

State/Province

Guangdong

ZIP/Postal Code

519000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhi-Gang Liu, MD, PhD

Phone

86-18627585860

First Name & Middle Initial & Last Name & Degree

Zhi-Gang Liu, MD, PhD

Facility Name

Wuzhou Red Cross Hospital

City

Wuzhou

State/Province

Guangxi

ZIP/Postal Code

543002

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jin-Hui Liang, MD

Phone

86-13878480806

First Name & Middle Initial & Last Name & Degree

Jin-Hui Liang, MD

12. IPD Sharing Statement

Learn more about this trial

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

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