Phase III Study of Camrelizumab in Combination With Chemotherapy in Recurrent/Metastatic Nasopharyngeal Carcinoma

A Phase III, Randomized, Double-Blind, Multi-center Study to Investigate the Efficacy and Safety of Camrelizumab+Gemcitabine+Cisplatin Versus Placebo+Gemcitabine+Cisplatin in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma

This study is a randomized, placebo-controlled, double-blind, multicenter phase III clinical study. Target population is patients with recurrent/metastatic nasopharyngeal carcinoma who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of camrelizumab in combination with gemcitabine and cisplatin with placebo in combination with gemcitabine and cisplatin in study population in China. camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Camrelizumab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebos

Detailed Description

In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Treatment cycles of chemotherapy will be at most 6 weeks which will be decided by investigators. Progression-free survival (PFS) determined by the Independent Review Committee (IRC) will be the primary outcome measures.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center of Sun-Yat Sen University (CCSYSU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤75 years;
2. Subjects with histopathological diagnosis of nasopharyngeal carcinoma;
3. Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment;
4. Has not received prior systemic treatment;
5. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
6. Subject must have a measurable target lesion based on RECIST v1.1;

Exclusion Criteria:

1. Allergic to monoclonal antibodies, any camrelizumab components, gemcitabine, cisplatin and other platinum drugs;

2. Prior therapy as follow:

   • Anti-PD-1 or anti-PD-L1;
   • Received last dose of anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within 4 weeks of the first dose of study medication;
   • Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone or equivalent for replacement therapy;
   • Received major operations or serious injuries within 4 weeks of the first dose of study medication;
3. Not recovered to ≤CTCAE 1 from adverse events (except for hair loss) due to a previously anti-tumor treatment;
4. Pregnancy or breast feeding;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camrelizumab + Gemcitabine + Cisplatin; subject will receive camrelizumab 200mg every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles	Drug: Camrelizumab; Maximum 6 cycles for combined therapy. Camrelizumab maintenance.; Other Names: SHR-1210; Drug: Gemcitabine; Maximum 6 cycles for combined therapy.; Other Names: Gemcitabine Hydrochloride for Injection; Drug: Cisplatin; Maximum 6 cycles for combined therapy.; Other Names: Cisplantin Injection
Active Comparator: Placebos + Gemcitabine + Cisplatin; subject will receive placebos every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles	Drug: Gemcitabine; Maximum 6 cycles for combined therapy.; Other Names: Gemcitabine Hydrochloride for Injection; Drug: Cisplatin; Maximum 6 cycles for combined therapy.; Other Names: Cisplantin Injection; Drug: Placebos; Maximum 6 cycles for combined therapy.; Other Names: Placebo - Concentrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee according to RECIST v1.1 or death from any cause, whichever occurs first.	up to 24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) assessed by investigators according to RECIST V 1.1	up to 24 month
Objective Response Rate (ORR)	The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1	up to 24 month
Disease Control Rate (DCR) Disease Control Rate (DCR)	The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1	up to 24 month
Duration of Response (DoR)	According to Recist v 1.1 accessed by investigators	up to 24 month
2 years Overall Survival (OS) rate	The percentage of patients overall survival in 2 years	up to 24 month
Adverse Events (AEs)	All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 4.03	up to 24 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antidrug Antibodies (ADAs)	To evaluate the incidence and titers of ADAs against camrelizumab	up to 24 month

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Li Zhang, MD, Cancer Center of Sun-Yat Sen University (CCSYSU); Study Director: Qing Yang, MD, Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): August 1, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: October 14, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Gemcitabine; Cisplatin; Nasopharyngeal Carcinoma; PD-1 Antibody
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: SHR-1210-III-308

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No