Metastatic Nasopharyngeal Carcinoma, Nasopharyngeal Carcinoma (NPC)
Conditions
Keywords
Metastatic Nasopharyngeal Carcinoma, Immunotherapy, Radiotherapy, Combined Modality Therapy, Tumor Immunity
Brief summary
The RADIANCE trial plans to enroll patients with chemotherapy-ineligible de novo metastatic nasopharyngeal carcinoma (AJCC 9th edition, TxNxM1). Participants will receive Radscopal radiotherapy, consisting of low-dose radiotherapy to the primary lesions and stereotactic body radiotherapy to distant metastatic lesions, in combination with sintilimab and ipilimumab. The study will evaluate the objective response rate of the primary lesions, systemic disease control as measured by progression-free survival and overall survival, and the safety and tolerability of this treatment regimen. The main questions this study aims to answer are: Does this treatment improve efficacy with acceptable safety in chemotherapy-ineligible patients? Does Radscopal radiotherapy enhance systemic antitumor immunity, and what is the Radscopal Response Rate? What clinical and immunological factors are associated with the Radscopal effect, and what mechanisms may underlie this effect?
Interventions
DRUGSintilimab
Sintilimab 200 mg will be administered by intravenous infusion once every 2 weeks, starting within 7 days after completion of stereotactic body radiotherapy, until unacceptable toxicity, disease progression, or for up to 6 months.
DRUGipilimumab
Ipilimumab 1 mg/kg will be administered by intravenous infusion once every 6 weeks for 2 cycles, beginning on the same day as the first sintilimab infusion.
RADIATIONRadscopal Radiotherapy
Participants will receive low-dose radiotherapy to the primary tumors at 8 Gy in 8 fractions. Stereotactic body radiotherapy will also be delivered to distant metastatic lesions at 24 Gy in 3 fractions.
Sponsors
Sun Yat-sen University
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age 18-80 years. * 2\. Histologically or cytologically confirmed de novo metastatic nasopharyngeal carcinoma (TxNxM1 according to AJCC 9th edition), with ≤10 measurable metastatic lesions. * 3\. At least one measurable nasopharyngeal lesion suitable for low-dose radiotherapy and at least one distant metastatic lesion suitable for stereotactic body radiotherapy. * 4\. ECOG performance status 0-2. * 5\. PD-L1 combined positive score (CPS) ≥1. * 6\. Chemotherapy-ineligible, including patients medically unsuitable for platinum-based chemotherapy or patients who refuse standard platinum-based chemotherapy after being fully informed. * 7\. Life expectancy ≥6 months. * 8\. Adequate organ function, including ANC ≥1.0 × 10\^9/L, platelets ≥75 × 10\^9/L, hemoglobin ≥80 g/L, ALT/AST ≤3 × ULN, bilirubin ≤2 × ULN, creatinine clearance ≥30 mL/min, and LVEF ≥45% or normal echocardiography. * 9\. No major surgery within 1 month before enrollment. * 10\. No immunosuppressive or immunomodulatory therapy within 1 month before immune checkpoint inhibitor treatment. * 11\. Written informed consent and ability to comply with study procedures and follow-up.
Exclusion criteria
* 1\. Age \<18 years. * 2\. \>10 metastatic lesions, meningeal metastasis, spinal cord compression, or lesions unsuitable for safe stereotactic body radiotherapy. * 3\. Other malignancy within 5 years, except cured basal cell carcinoma, squamous cell carcinoma of the skin, papillary thyroid carcinoma, or cervical carcinoma in situ. * 4\. Prior systemic immune checkpoint inhibitor therapy or prior nasopharyngeal radiotherapy. * 5\. Active hepatitis B infection, defined as HBsAg positivity with HBV DNA \>200 IU/mL or \>1000 copies/mL. * 6\. Positive hepatitis C virus antibody. * 7\. Active, known, or suspected autoimmune disease, except type 1 diabetes, hypothyroidism requiring only hormone replacement, or skin disorders not requiring systemic treatment. * 8\. Systemic corticosteroids equivalent to \>10 mg prednisone daily or other immunosuppressive therapy within 28 days before informed consent, except low-dose, inhaled, or topical corticosteroids. * 9\. Active tuberculosis, active tuberculosis within the previous year, or prior active tuberculosis without documented adequate anti-tuberculosis treatment. * 10\. History of interstitial lung disease. * 11\. Uncontrolled diabetes mellitus (fasting blood glucose \>13.9 mmol/L). * 12\. Live vaccine within 30 days before informed consent or planned live vaccination. * 13\. Known allergy to macromolecular protein preparations or to any component of sintilimab or ipilimumab. * 14\. HIV infection. * 15\. Any condition that may affect participant safety or compliance, including uncontrolled cardiovascular disease, active infection requiring systemic treatment, psychiatric illness, severe cognitive impairment, suicidal tendency, or relevant psychological, family, or social factors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of Primary Lesions | 6 months | The proportion of participants with confirmed complete response or partial response in measurable primary lesions (nasopharyngeal and neck), assessed according to RECIST version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Lesion Irradiation Type | 6 months | The proportion of lesions achieving complete response or partial response among stereotactic body radiotherapy-treated, low-dose radiotherapy-treated, and non-irradiated lesions according to RECIST version 1.1. |
| Disease Control Rate (DCR) | 6 months | The proportion of patients achieving complete response, partial response, or stable disease according to RECIST version 1.1. |
| Duration of Response (DoR) | 1 year | The time from first documented complete response or partial response to disease progression or death from any cause. |
| One-Year Progression-Free Survival (PFS) | 1 year | Calculated from enrollment to the date of disease progression or death from any cause, whichever occurred first. |
| One-Year Overall Survival (OS) | 1 year | Calculated from enrollment to the date of death from any cause. |
| Adverse Events (AEs) and serious adverse events (SAEs) | 1 year | Graded according to CTCAE version 5.0. |
| Quality of Life (QoL): EORTC QLQ-C30 | 1 year | Change in QoL from baseline will be assessed using the EORTC QLQ-C30 questionnaire. The questionnaire includes functional scales, symptom scales, a global health status scale, and single-item symptom scales. Scores will be calculated according to the EORTC scoring manual. |
| Quality of Life (QoL): EORTC QLQ-HN35 | 1 year | Change in head and neck cancer-specific QoL from baseline will be assessed using the EORTC QLQ-HN35 questionnaire. Scores will be calculated according to the EORTC scoring manual. |
Countries
China
Contacts
CONTACTYanping Mao, MD, PhD
PRINCIPAL_INVESTIGATORYanping Mao, MD, PhD
Sun Yat-Sen University Cancer Center
Outcome results
None listed