Comparing targeted therapy and chemotherapy with immunotherapy for patients with resistant nasopharyngeal carcinoma

Antiangiogenic Therapy or Chemotherapy Combined With PD-1 Inhibitor Versus Standard Chemotherapy for PD-1 Inhibitor Refractory R/M NPC

This study is testing whether combining targeted therapy or chemotherapy with a new type of immunotherapy can help patients with stubborn nasopharyngeal cancer feel better and improve their treatment outcomes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05549466 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of combining anti-angiogenic drugs or standard chemotherapy with PD-1 inhibitors in patients with recurrent or metastatic nasopharyngeal carcinoma who have become resistant to PD-1 inhibitors. It aims to determine which treatment regimen offers the most benefit to these patients. The study includes patients who have previously undergone platinum-based chemotherapy and have measurable lesions. The goal is to address the urgent clinical challenge of managing resistance to immunotherapy in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with recurrent or metastatic nasopharyngeal carcinoma who have progressed after treatment with PD-1 inhibitors and platinum-based chemotherapy.

Not a fit: Patients with recurrent lesions suitable for radical treatment or those who have previously received more than two lines of systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with PD-1 inhibitor refractory nasopharyngeal carcinoma.

How similar studies have performed: Previous studies have shown promising results with similar combinations of anti-angiogenic drugs and immunotherapy, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Male or female; 18-70 years of age;
2. Had histopathologically confirmed nonkeratinizing recurrent/metastatic NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary).
3. ECOG performance status of 0 or 1.
4. Progression after previous treatment with platinum-based dual-drug chemotherapy.
5. Progression after previous treatment with PD-1 inhibitors.
6. Experieced at least 1 line systemic therapy.
7. Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.
8. Adequate organ function assessed by laboratory parameters during the screening period
9. Life expectancy more than 12 weeks.
10. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

1. Recurrent lesions suitable for radical treatment (radiotherapy or surgery).
2. Previous treatment over 2 lines.
3. Patients who had previously received one of the three chemotherapy drugs and were randomly assigned to single-agent chemotherapy (control group) were not eligible to reuse the same treatment in this study. In addition, patients who had previously received all three chemotherapy agents for R/M lesions were excluded from the study.
4. Prior use of any anti-VEGF(R) agents.
5. Patients with other malignancies.
6. Patients with nasopharyngeal necrosis found by endoscope before enrollment or with a \> 50% chance of nasopharyngeal necrosis according to the risk prediction model: 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 radiotherapy and nasopharyngeal radiotherapy within 1 year before enrollment.
7. 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).
8. 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.
9. Patients with known or suspected autoimmune diseases including dementia and seizures.
10. Multiple factors affecting the absorption of oral medications (e.g., dysphagia, chronic diarrhea, and bowel obstruction).
11. An excessive dose of glucocorticoids given within 4 weeks before enrollment.
12. Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
13. Patients with active pulmonary tuberculosis (TB) receiving anti-TB treatment or who have received anti-TB treatment within 1 year prior to screening.
14. 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).
15. Any anti-infective vaccines such as influenza vaccine, varicella vaccine, etc., within 4 weeks before enrollment.
16. Women of childbearing age with a positive pregnancy test and lactating women.
17. Special attention: Patients with active bleeding, ulcers, and bowel perforations within 30 days after major surgery with tumors in close proximity to the internal carotid artery or other major vessels, and those at risk of major bleeding are prohibited.
18. Patients considered unsuitable for inclusion.

Where this trial is running

Guangzhou, Guangdong

• Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Ming-yuan Chen, MD, PhD — Sun Yat-sen University
• Study coordinator: Ming-Yuan Chen, MD, PhD

Conditions: Nasopharyngeal Carcinoma