Reduced-dose RT With/Without CCT Versus Standard CCRT for High-risk LANPC Who Achieved CR Post Induction Chemotherapy

NCT06092957 | Recruiting Phase 3 DMC

• 1 other identifier: SYSUCC-CMY-2023-09-25
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective trial aims to enroll patients with high-risk stage III-IVA (AJCC 8th, except T3N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Under the condition of full course of PD-1/PD-L1 blockades, patients who achieved both radiological and biological complete response after 3 cycles of platinum-based chemotherapy plus PD-1/PD-L1 blockades will be randomized in a 1:1:1 ratio to receive reduced-dose radiotherapy (60Gy/30F) alone or reduced-dose radiotherapy plus concurrent chemotherapy or standard dose radiotherapy (70Gy/33F) with concurrent chemotherapy. To solve the urgent problem of whether patients with high-risk advanced nasopharyngeal carcinoma are suitable for downgrade treatment.

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 (3)

Induction chemotherapy plus conventional concurrent chemoradiotherapy

ACTIVE COMPARATOR

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

Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

EXPERIMENTAL

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

Induction chemotherapy plus reduced-dose radiotherapy alone

EXPERIMENTAL

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

Interventions

Cisplatin-based induction chemotherapy DRUG

Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy including GP, TP, and TPF regimen.

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus reduced-dose radiotherapy alone; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

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 reduced-dose radiotherapy alone; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Reduced-dose IMRT RADIATION

GTVnx:60Gy/30F/2.0Gy，CTV1:54Gy/30F/1.8Gy，CTV2:48Gy/30F/1.6Gy

Induction chemotherapy plus reduced-dose radiotherapy alone; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Standard-dose IMRT RADIATION

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

Induction chemotherapy plus conventional concurrent chemoradiotherapy

Concurrent Chemotherapy DRUG

Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Induction chemotherapy plus conventional concurrent chemoradiotherapy; Induction chemotherapy plus reduced-dose radiotherapy and concurrent chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 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, except T3N0).
• Patients who achieved both radiological and biological CR according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy, and EBV DNA load =0 copies/mL (or lower than the test line) after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
• Eastern Cooperative Oncology Group performance status ≤1.
• 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 PR or SD or PD or EBV DNA load of \>0 copies/mL 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.
• Patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (other than diagnostic treatment).
• Subjects 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.
• Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease).
• Grade ≥2 epistaxis (defined as the need for medical intervention such as nasal tamponade, cautery, topical vasoconstrictors, according to CTCAE 5.0) within 1 month prior to enrollment; Macroscopic hemoptysis or hematemesis) is defined as ≥1/2 teaspoon of bright red blood, or a blood clot with little/no sputum on each cough). (Patients with mixed sputum-blood occasionally may be enrolled).
• 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.
• Patients currently take warfarin, heparin, aspirin (\> 325 mg/day) or other NSAIDs known to inhibit platelet function, ticlopidine, clopidogrel, or cilostazol. (Patients can be enrolled if they discontinue these drugs 10 days prior to the commence of study and meet the requirements of coagulation in the enrollment criteria).
• Patients with other malignancies (except for cervical cancer, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer, and ductal carcinoma in situ who have undergone curative treatment).
• Has a known history of interstitial lung disease.
• Known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
• Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
• Has active autoimmune disease or any condition that requires systemic corticosteroid or immunosuppressive therapy, 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. Subjects with the following conditions will not be excluded from this study: asthma that requires intermittent use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions may be made with medical monitor approval.
• 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).

Sponsors & Collaborators

• Sun Yat-sen University: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Second Affiliated Hospital, Sun Yat-Sen University: collaborator
• The fifth Affiliated Hospital of Guangzhou Medcial University: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator
• Hunan Cancer Hospital: collaborator
• Tongji Hospital: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, 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: October 16, 2023
• First Posted: October 23, 2023
• Study Start: October 9, 2023
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): October 30, 2031
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

CN (1)