Clinical trial NCT05431764: Whole-target Consolidation Therapy Under Systemic Therapy for Oligometastatic Nasopharyngeal Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: Oligometastatic Nasopharyngeal Carcinoma
Immunotherapy
Stereotactic Body Radiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-06-24
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Median progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Disease control rate (DCR)
timeFrame: 2 years
measure: Median overall survival (OS)
timeFrame: 2 years
measure: Adverse events
timeFrame: 2 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
timeFrame: 2 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: 2 years
measure: Duration of response (DoR)
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ming-Yuan Chen, MD, PhD
role: STUDY_CHAIR
References: