Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma

Whole-target Consolidation Therapy After Standard Chemotherapy for Initial Diagnosed Distant Metastatic Nasopharyngeal Carcinoma Under Full-course Immunotherapy: An Open-Label, Single Center, Nonrandomized, Phase 2 Study

In this exploratory clinical trial, patients with newly diagnosed distant metastatic nasopharyngeal carcinoma were treated with gemcitabine+ cisplatin+PD-1 inhibitor regimen followed by whole-target radiotherapy (IMRT for local regional lesion, SBRT for distant metastasis) and PD-1 inhibitor long-term maintenance regimen. To investigate the efficacy and safety of "whole target" radiotherapy combined with immuno-maintenance therapy.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Camrelizumab, gemcitabin, cisplatin; Radiation: Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy

Detailed Description

This exploratory clinical trial will evaluate tumor control rate, survival, and safety of newly diagnosed distant metastatic nasopharyngeal carcinoma by further adding local regional IMRT, distant metastatic SBRT and immuno-maintenance therapy to the standard regimen of gemcitabine+ cisplatin+ PD-1 inhibitor (historical data). To explore whether the "full target" model can be a better comprehensive therapy for the initial diagnosed distant metastatic nasopharyngeal carcinoma in the era of immunotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female; 18-70 years of age.
2. Had histopathologically confirmed nonkeratinizing metastatic NPC that was diagnosed as stage IVb NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary).
3. Patients who had not received anti-tumor therapy for nasopharyngeal cancer before this clinical trial.
4. Patients evaluated to have a partial response (PR) or stable disease (SD) by head and neck MRI and PET/CT after 3 months of locoregional radiotherapy, and the metastatic lesions were assessed as oligometastatic lesions (the number of total metastatic lesions no more than 5 and the number of metastatic lesions within a single organ no more than 3).
5. Stereotactic body radiotherapy applicable for all metastatic lesions according to MDT.
6. ECOG performance status of 0 or 1.
7. Maximum diameter of brain metastatic lesion no more than 3cm.

8. Maximum diameter of metastatic lesion (brain excluded) no more than 5cm.

   • Maximum diameter of bone metastatic lesion no more than 6cm if attending doctor decides it is safe to apply the treatment.
9. Life expectancy more than 6 months.

Exclusion Criteria:

1. History of severe hypersensitivity to any ingredient of PD-1/PD-L1 or other monoclonal antibody.
2. chemotherapy (cytotoxic or molecular targeted) within 4 weeks before stereotactic body radiotherapy.
3. Imageological evidence for spinal cord compression, or tumor less than 3mm away from spinal cord.
4. Patient with brain metastasis who needs decompression surgery.
5. Other malignancy or malignant hydrothorax.
6. Concurrent known or suspicious autoimmune disease, including dementia and epilepsy.
7. CHD no less than grade 2, arrhythmia (QTc interval over 450ms for male and 470ms for female) or cardiac insufficiency.
8. Use of large dose corticosteroids within 4 weeks before study drug administration.
9. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids.
10. Active tuberculosis (TB), anti-TB treatment is ongoing or within 1 year prior to screening
11. Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy.
12. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive.
13. Received any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment.
14. Pregnancy or lactation.
15. Other ineligible patients according to attending doctor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Camrelizumab Plus Stereotactic Body Radiotherapy; Patients were treated with gemcitabine, cisplatin and camrelizumab for 6 cycles, followed by whole-target radiotherapy (IMRT for locoregional lesion and SBRT for oligometastatic lesions) and camrelizumab maintenance therapy.

Drug: Camrelizumab, gemcitabin, cisplatin; Patients receive gemcitabine (1000 mg/m² d1,8), cisplatin (80mg/m² d1), and camrelizumab (200mg, iv drip for over 60min) every 3 weeks for 6 cycles before locoregional radiotherapy.; Other Names: PD-1 inhibitor; Radiation: Stereotactic Body Radiotherapy, Intensity modulated-radiotherapy; IMRT: 5 fractions per week for 6 weeks to a total dose of 70 Gy and 33 fractions to the primary tumor. SBRT: 3 months after locoregional IMRT, patients receive SBRT for all oligometastatic lesions as radical therapy to control the disease and reduce any potential adverse impact to living quality. The dosage is based on published clinical studies. Camrelizumab (200mg, iv drip for over 60min) every 2 weeks began on the first day of IMRT until an intolerable toxicity, or disease progression, or withdrawal of consent, or the investigator determines that he or she has to withdraw from treatment, or has been treated for up to 2 years.; Other Names: SBRT; IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression-free survival (PFS)	Progression-free survival is calculated from the date of randomization to the date of death of any cause or the first progress at any site, censored on the last date of tumor evaluation if no progress has happened.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate is the rate of patients achieving complete response or partial response for a certain period of time after intervention.	2 years
Disease control rate (DCR)	Disease control rate is the rate of patients achieving complete response, partial response or stable disease for at least 4 weeks after intervention.	2 years
Median overall survival (OS)	Overall survival is calculated from the date of randomization to the date of death of any cause, censored on the last date of known survival if no death has happened	2 years
Adverse events	NCI-CTC5.0 and RTOG standards are adopted, and acute subjective toxicity, acute objective toxicity and late subjective toxicity are included.	2 years
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, and after treatment.	2 years
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.	2 years
Duration of response (DoR)	Defined as the time from first documentation of objective response to radiological disease progression.	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 20, 2022
• Primary Completion (Anticipated): June 20, 2025
• Study Completion (Anticipated): June 20, 2026

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 19, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): June 24, 2022
• Last Update Submitted That Met QC Criteria: June 19, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; Stereotactic Body Radiotherapy; Oligometastatic Nasopharyngeal Carcinoma
• 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; Cisplatin; Immune Checkpoint Inhibitors
• Other Study ID Numbers: SYSUCC-SBRT2022

Drug and device information, study documents

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