Under Whole-course of Immunotherapy, Gradient Fractionated RT with CCT Versus CFRT with CCT for LANPC Who Achieved PR Post Induction Chemotherapy.

NCT06675214 | Recruiting Phase 3 DMC

• 1 other identifier: ZDWY.BYAFZZX.074
• Study Type: interventional
• Target: 586
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective trial aims to enroll patients with stage III-IVA (AJCC 8th,) locoregionally advanced nasopharyngeal carcinoma (LANPC). Under the condition of full course of PD-1/PD-L1 blockades, patients who achieved radiological partial response after 3 cycles of platinum-based chemotherapy plus PD-1/PD-L1 blockades will be randomized in a 1:1 ratio to receive gradient radiotherapy (reducing the irradiation dose of PET-CT areas without metabolic abnormalities, while maintaining adequate irradiation dose of areas with metabolic abnormalities) or standard dose radiotherapy with concurrent chemotherapy. It is expected to provide a new therapeutic option for locally advanced nasopharyngeal carcinoma at moderate risk.

Conditions

Nasopharyngeal Carcinoma; De-escalation Therapy

Outcome Measures

Primary Outcomes (1)

• Progress-Free Survival (PFS)

  Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (7)

• Overall Survival (OS)

  3 years

• Locoregional Relapse-Free Survival (LRRFS)

  3 years

• Distant Metastasis-Free Survival (DMFS)

  3 years

• The proportion of patients with treatment related acute complications

  1 year

• The proportion of patients with treatment related late complications

  3 years

Study Arms (2)

Induction chemotherapy plus conventional concurrent chemoradiotherapy

ACTIVE COMPARATOR

Drug: Full course of PD-1/PD-L1 blockades; Drug: Cisplatin-based induction chemotherapy; Radiation: Standard-dose IMRT; Drug: Concurrent Chemotherapy

Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

EXPERIMENTAL

Drug: Full course of PD-1/PD-L1 blockades; Drug: Cisplatin-based induction chemotherapy; Radiation: Gradient Fractionated IMRT; Drug: Concurrent Chemotherapy

Interventions

Full course of PD-1/PD-L1 blockades DRUG

a) Camrelizumab 200mg, b) Toripalimab 240mg, or c) Adebrelimab 1200mg will be started on day 1 of induction chemotherapy and given every 3 weeks for up to 12 cycles, or until intolerable toxicity, or disease progression or withdrawal from the treatment.

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

Cisplatin-based induction chemotherapy DRUG

Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy.

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

Standard-dose IMRT RADIATION

GTVnx/nd:69.96Gy/33Fr/2.12Gy CTV1: 60.60Gy/33Fr/1.82y CTV2: 54.12Gy/33Fr/1.64Gy

Induction chemotherapy plus conventional concurrent chemoradiotherapy

Gradient Fractionated IMRT RADIATION

GTVresidue: 68Gy/30Fr/2.27Gy GTVmcr: 60Gy/30F/2Gy CTV1:54Gy/30F/1.8Gy CTV2: 48GY/30F/1.60Gy

Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

Concurrent Chemotherapy DRUG

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Tumor staged as III-IVA (AJCC 8th).
• Patients who achieved partial response according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
• Eastern Cooperative Oncology Group performance status ≤1.
• Age: 18-65 years old.
• Adequate organ function:
• Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Adequate liver and kidney function: Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.; creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the upper normal limit.
• Patients must be informed of the investigational nature of this study and give written informed consent.

You may not qualify if:

• Patients who are evaluated as CR or SD or PD after 3 cycles of induction therapy of platinum-based chemotherapy plus PD-1/PD-L1 blockades.
• The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
• The images of PET-CT and enhanced MRI/CT before induction chemotherapy showed necrotic foci in the center of primary tumors or regional lymph nodes.
• The metabolic changes shown by PET-CT images after induction chemotherapy were inconsistent with the changes in the extent of tumor invasion shown by anatomical images such as enhanced MRI/CT.
• The primary and/or cervical metastases of patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (except diagnostic treatment).
• Has a known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
• Has a known or suspected history of autoimmune diseases, including dementia and seizures.
• Patients with recurrence, distant metastasis and other malignant tumors.
• Severe heart disease, lung dysfunction, heart function, lung function below grade 3 (including grade 3)
• Patients who underwent anti-PD-1 /PD-L1 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway) and anti-angiogenic drugs.
• 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).
• Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
• Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
• Has received a live vaccine; or a systematic glucocorticoid therapy ; or any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) ; any Chinese anti-tumor herbs within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, 519000, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Ming-Yuan Chen, MD,PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming-Yuan Chen, MD,PhD

CONTACT

+86-20-87343361; chenmy@sysucc.org.cn

Rui You, MD,PhD

CONTACT

+86-13580439820; yourui@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2024
• First Posted: November 5, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2030
• Last Updated: November 5, 2024

Record last verified: 2024-07

Locations

CN (1)