Clinical trial NCT05340270: PD-1 Inhibitor Plus GP as Neoadjuvant Therapy for Locoregionally Advanced Nasopharyngeal Carcinoma
Official title: PD-1 Inhibitor Plus GP Chemotherapy as Neoadjuvant Therapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II, Multicenter, Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Neoadjuvant Therapy
PD-1 Inhibitor
Lead sponsor: Guangxi Medical University
Sponsor class: OTHER
Collaborators: name: Hainan People's Hospital
name: Wuzhou Red Cross Hospital
name: First People's Hospital of Yulin
name: Fourth Affiliated Hospital of Guangxi Medical University
name: Guigang People's Hospital
name: Wuhan Union Hospital, China
name: Yunnan Cancer Hospital
name: LiuZhou People's Hospital
name: Afﬁliated Hospital of North Sichuan Medical College
First posted: 2022-04-22
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this Phase II, Multicenter, Randomized Controlled Clinical Trial is to evaluate the efficacy and safety of PD-1 inhibitor Plus GP chemotherapy as Neoadjuvant Therapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma.

Detailed description: Induction chemotherapy plus concurrent chemoradiotherapy has the IIA evidence and the gemcitabine plus cisplatin (GP) regimen has the I evidence in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). More and more evidence shows that immunotherapy combined with chemotherapy has a synergistic effect in treating tumors. GP chemotherapy combined with PD-1 inhibitor has achieved the initial effect in NPC. With the development of radiotherapeutic techniques and equipment as well as advances in treatment modalities, the 5-year overall survival of patients with non-disseminated NPC has exceeded 80%. But there are still about 20-30% of NPC patients who experienced recurrence or metastasis after radical chemoradiotherapy, especially locoregionally advanced patients. In order to improve their survival, we conduct this clinical trial to determine whether GP chemotherapy combined with PD-1 inhibitor as neoadjuvant therapy can improve the failure-free survival rate of locoregionally advanced NPC patients and provide new evidence for their neoadjuvant therapy of them.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma(WHO II/III).
2. Original clinical staged as T4NanyM0 or TanyN2-3M0 (according to AJCC 8th edition), with no evidence of distant metastasis.
3. Eastern Cooperative Oncology Group performance status ≤1.
4. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L, and platelet count ≥100×10e9/L.
5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤1.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
6. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
7. Patients must be informed of the investigational nature of this study and give written informed consent.
8. Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.

Exclusion Criteria:

1. Age \> 65 or \< 18.
2. Receiving radiotherapy or chemotherapy or targeted therapy or immunotherapy previously.
3. Severe cerebrovascular disease/canker/psychosis.
4. Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
5. Has any condition that required systemic corticosteroid (equivalent to prednisone \>10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients who received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
6. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
7. Suffering from active infection diseases and in need of treatment.
8. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
9. Pregnant or breastfeeding.
10. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer and papillary thyroid carcinoma.
11. Has known allergy to large molecule protein products or any compound of PD-1 antibody.
12. Has a known history of the human immunodeficiency virus (HIV) infection.
13. Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Primary outcomes:
measure: Failure-free survival
timeFrame: up to 24 months
Secondary outcomes:
measure: Complete Response (CR)
timeFrame: up to 9 weeks
measure: Overall survival
timeFrame: up to 24 months
measure: Locoregional failure-free survival(LRRFS)
timeFrame: up to 24 months
measure: Distant metastasis-free survival(DMFS)
timeFrame: up to 24 months
measure: Adverse events (AEs)
timeFrame: up to 24 months
measure: Quality of life（QOL）
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: RENSHENG WANG, MD
role: PRINCIPAL_INVESTIGATOR
References: