Clinical trial NCT06092957: Reduced-dose RT With/Without CCT Versus Standard CCRT for High-risk LANPC Who Achieved CR Post Induction Chemotherapy
Official title: Reduced-dose Radiotherapy With/Without Concurrent Chemotherapy Versus Standard Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma Who Achieved Complete Response After Induction Chemotherapy Plus Immunotherapy: a Randomized, Open-label, Multicenter, Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
De-escalation Therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Guangdong Provincial People's Hospital
name: Second Affiliated Hospital, Sun Yat-Sen University
name: The fifth Affiliated Hospital of Guangzhou Medcial University
name: Zhongshan People's Hospital, Guangdong, China
name: Hunan Cancer Hospital
name: Tongji Hospital
First posted: 2023-10-23
Enrollment: 504
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
2. Tumor staged as III-IVA (AJCC 8th, except T3N0).
3. 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.
4. Eastern Cooperative Oncology Group performance status ≤1.
5. 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.
6. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. 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.
2. The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
3. Patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (other than diagnostic treatment).
4. 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.
5. Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease).
6. 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).
7. 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.
8. 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).
9. 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).
10. Has a known history of interstitial lung disease.
11. Known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
12. Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
13. 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.
14. Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
15. 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).
16. Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
17. 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.
18. Pregnancy or breastfeeding.
19. Other patients who were considered unsuitable by the treating physicians.

Primary outcomes:
measure: Progress-Free Survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Locoregional Relapse-Free Survival (LRRFS)
timeFrame: 3 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 3 years
measure: The proportion of patients with treatment related acute complications
timeFrame: 1 year
measure: The proportion of patients with treatment related late complications
timeFrame: 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
timeFrame: 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ming-Yuan Chen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: