Gemcitabine and Camrelizumab Plus Apatinib Versus Cisplatin in First-line Treatment of RM-NPC

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05854849

Collaborator

(none)

244

Enrollment

Location

Arms

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to explore a new, more effective and tolerable treatment regimen for patients with advanced recurrent/metastatic nasopharyngeal carcinoma. Specifically, we plan to conduct a phase III randomized controlled clinical trial based on the standard treatment of "GP + PD-1 mAb", replacing cisplatin with apatinib to achieve "platinum-free" therapy and reduce toxicity. In addition, we will investigate the efficacy of using apatinib in combination with PD-1 mAb compared to PD-1 mAb monotherapy to further improve treatment outcomes. The ultimate goal is to provide a new and reliable treatment modality for patients with advanced recurrent/metastatic nasopharyngeal carcinoma and guide clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Drug: Camrelizumab Drug: Gemcitabine Drug: Cisplatin Drug: Apatinib	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

244 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Phase 3 Clinical Trial of Gemcitabine and Camrelizumab Plus Apatinib Versus Cisplatin in First-line Treatment of Recurrent/Metastatic Nasopharyngeal Carcinoma

Actual Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GAP	Drug: Camrelizumab 200mg, D1, Q3W, iv drip. Drug: Gemcitabine 1000mg/m2, Day 1 and Day 8, Q3W, iv drip, maximum 6 cycles. Drug: Apatinib 250mg, PO, QD
Active Comparator: GPP	Drug: Camrelizumab 200mg, D1, Q3W, iv drip. Drug: Gemcitabine 1000mg/m2, Day 1 and Day 8, Q3W, iv drip, maximum 6 cycles. Drug: Cisplatin 80 mg/m2, D1, Q3W, iv drip, maximum 6 cycles.

Arm

Intervention/Treatment

Experimental: GAP

Drug: Camrelizumab

200mg, D1, Q3W, iv drip.

Drug: Gemcitabine

1000mg/m2, Day 1 and Day 8, Q3W, iv drip, maximum 6 cycles.

Drug: Apatinib

250mg, PO, QD

Active Comparator: GPP

Drug: Camrelizumab

200mg, D1, Q3W, iv drip.

Drug: Gemcitabine

1000mg/m2, Day 1 and Day 8, Q3W, iv drip, maximum 6 cycles.

Drug: Cisplatin

80 mg/m2, D1, Q3W, iv drip, maximum 6 cycles.

Outcome Measures

Primary Outcome Measures

Progression-free survival [2 years]
the time from treatment initiation to disease progression or death from any cause.

Secondary Outcome Measures

Overall survival [2 years]
the survival time until death from any cause
Objective response rate [2 years]
the proportion of patients with complete response (CR) or partial response (PR) according to RECIST v1.1
Disease control rate [2 years]
the proportion of patients who achieved CR, PR, or stable disease
Duration of response [2 years]
the time from the first evidence of response to disease progression or death
Safety evaluation [2 years]
incidence of adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female; 18-70 years of age;
Had histopathologically confirmed nonkeratinizing recurrent/metastatic NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary; locoregional recurrent lesion unfit for local treatment).
Did not receive any systemic treatment for recurrent and metastatic lesions. (Previous radiotherapy, induction chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy should have been completed at least 6 months prior to treatment)
ECOG performance status of 0 or 1.
Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.
Adequate organ function assessed by laboratory parameters during the screening period
Life expectancy more than 12 weeks.
Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

Patients with a high risk of nasopharyngeal necrosis: ① Patients with recurrent stage T3-4 received two courses of radiotherapy before enrollment, or received nasopharyngeal radiotherapy within 1 year before enrollment; ② Patients with recurrent T1-2 stage had received two courses of nasopharyngeal radiotherapy and the last radiotherapy within 1 year before enrollment.
Patients with other malignancies (except for cervical cancer, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer, and ductal carcinoma in situ who have undergone curative treatment).
Special attention: Patients with active bleeding, ulcers, bowel perforations, and major surgery within 30 days; tumors in close proximity to the internal carotid artery or other major vessels, and those at risk of major bleeding. Patients with or previous with serious hemorrhage (bleeding >30 ml within 3 months), haemoptysis (> 5 ml within 4 weeks) of thromboembolic events within 12 months (including stroke events and/or transient ischemic attack).
Patients with hypertension who cannot be reduced to the normal range by antihypertensive drug treatment (systolic blood pressure > 140 mmHg/diastolic blood pressure > 90 mmHg), patients with ≥ grade II coronary heart disease, arrhythmia (including QTc interval prolongation > 450 ms in men and > 470 ms in women) and cardiac insufficiency.
Patients with known or suspected autoimmune diseases including dementia and seizures.
Multiple factors affecting the absorption of oral medications (e.g., dysphagia, chronic diarrhea, and bowel obstruction).
An excessive dose of glucocorticoids given within 4 weeks before enrollment.
Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
HIV positive; HBsAg positive and HBV DNA copy number positive (quantitative detection ≥ 1000 cps/ml); chronic hepatitis C with blood screening positive (HCV antibody positive).
Women of childbearing age with a positive pregnancy test and lactating women.