PD-1 Inhibitors Plus Chemoradiotherapy for Metastatic Nasopharyngeal Carcinoma: an Open-label Single-arm, Phase II Trial

NCT05520814 | Unknown Phase 2 DMC

• 1 other identifier: Ahead-NC-202207
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

programmed cell death-1 (PD-1) inhibitors has been recommended as the first-line treatment for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), but progression-free survival (PFS) and overall survival (OS) was still unsatisfactory. Basic studies have already confirmed PD-1 inhibitors had concurrent synergistic effect with chemotherapy and radiotherapy. Few studies concerned about the treatment pattern for concurrent PD-1 inhibitors combination with chemoradiation for R/M NPC. There was still much uncertainties about the timing, fraction dose and total dose for PD-1 inhibitors combination with radiation. Therefore, we aimed to explore the substantial effect and toxicity of this new pattern for R/M NPC.

Conditions

Nasopharyngeal Carcinoma; PD-1 Inhibitors; Chemoradiotherapy

Keywords

PD-1 inhibitors; concurrent; metastatic; nasopharyngeal carcinoma; chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Three months after the end of radiotherapy, the proportion of patients whose tumors shrink to a certain amount and remain for a certain time, including those with complete remission (CR) + partial remission (PR).

  3 months post radiotherapy

Secondary Outcomes (3)

• overall survival (OS) rate

  1, 2-year

• Progression-free survival (PFS) rate

  1,2-year

• Disease Control Rate(DCR)

  3 months post radiotherapy

Study Arms (1)

metastatic nasopharyngeal carcinoma

EXPERIMENTAL

Drug: PD-1 inhibitors; Radiation: chemoradiotherapy

Interventions

PD-1 inhibitors DRUG

treprizumab injection 240mg / carrilizumab injection 200mg / Tirelizumab injection 200mg \* q21d (until the disease progresses, intolerable toxicity or the investigator / subject decides to withdraw from the study, and the duration of PD-1 inhibitor is not more than 96 weeks)

metastatic nasopharyngeal carcinoma

chemoradiotherapy RADIATION

Chemotherapy： 1. GP: gemcitabine 1g/m2 D1, 8 Cisplatin 80 mg/m2 d1 \* Treatment courses every 3 weeks 2. Cisplatin 80mg/m2 d1 or carboplatin area under the curve 5mg/ml/min \* Treatment courses every 3 weeks Radiotherapy： All the metastatic lesions received radiation dose from 30 to 60Gy according to different metastatic sites.

metastatic nasopharyngeal carcinoma

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the trial and sign the informed consent for the study in writing.
• Age ≥ 18 years old (when signing the informed consent for this study).
• Metastatic disease after primary standard treatment (patients who had metastatic diseases over six months after treatment)
• Metastatic lesions are not suitable for surgery.
• According to recist1.1 evaluation criteria, there are measurable lesions (1-5 measurable lesion).
• The physical state of the Eastern Cooperative Oncology Group (ECoG) was 0-1.
• Tumor tissue can be provided for PD-L1 expression detection: newly obtained biopsy (within 90 days before the start of study treatment) is preferred. If biopsy tissue cannot be provided for detection, archived tissue wax block can be provided for post-section detection.
• Urine pregnancy test was negative (female), and contraceptive measures were taken from the trial period to 3 months after the end of the trial.
• The function of main organs is normal, and the blood routine examination shall meet the following standards: WBC ≥ 4.0 × 109/L，ANC≥2.0 × 109/L， PLT≥100 × 109 / L, Hb ≥ 90g / L (no blood transfusion and blood products within 14 days, no correction with G-CSF and other hematopoietic stimulating factors); Biochemical examination shall meet the following standards: TBIL ≤ 2.0 × ULN，ALT、AST≤2.5 × ULN, bun and cre ≤ 1.5 × The clearance rate of ULN or endogenous creatinine ≥ 60ml / min (Cockcroft Gault formula); Good coagulation function: defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; If the subject is receiving anticoagulant treatment, as long as Pt is within the proposed scope of use of anticoagulant drugs; The myocardial enzyme spectrum was within the normal range.
• According to the judgment of the investigator, the patient was considered to be able to comply with the protocol.

You may not qualify if:

• Locally advanced nasopharyngeal carcinoma has disease progression (PD) within 6 months after systemic treatment.
• It is known that any component of the investigational drug or preparation has caused severe hypersensitivity, including severe hypersensitivity to other monoclonal antibodies, gemcitabine, taxol, fluorouracil, platinum and other related compounds (NCI ctcaev5.0 ≥ grade 3).
• According to the criteria of common adverse event terminology (NCI ctcaev5.0), there were peripheral neuropathy ≥ grade 2.
• Other malignant tumors occurred within 5 years or present at the same time.
• Interstitial lung disease or non communicable pneumonia (including past history and present condition); Local interstitial pneumonia induced by radiotherapy is excluded.
• Have uncontrolled systemic diseases, including diabetes, hypertension, acute lung disease, etc.
• Active infections requiring systemic treatment, including active tuberculosis.
• Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage.
• There are obvious cardiovascular diseases, heart failure classified as grade 2 or above by the New York Heart Association (NYHA), previous myocardial infarction within 3 months, unstable arrhythmia (including QT interval ≥ 480 MS) or unstable angina pectoris.
• Active central nervous system metastasis and / or cancerous meningitis (before the first administration, except for patients with stable brain metastases: subjects with brain metastases who have received previous treatment can participate in the study, provided that they are clinically stable for at least 2 weeks, there is no evidence of new or expanded brain metastases, and steroids are stopped 3 days before the administration of the study drug. Except for subjects with asymptomatic brain metastases: they have no neurological symptoms, do not need corticosteroids, and have no lesions \> 1.5cm, and they need regular brain tests as disease sites Imaging examination.)
• Active hepatitis B or C, meeting any of the following conditions: hepatitis B virus deoxyribonucleic acid (HBV DNA) in peripheral blood is positive (the result is greater than the detection limit of the analysis method); Hepatitis C virus RNA (HCV RNA) in peripheral blood was positive (the result was greater than the detection limit of the analysis method).
• Patients with a history of immune deficiency, including HIV positive and / or other acquired and congenital immune deficiency diseases, and / or patients with a history of organ transplantation.
• Active autoimmune diseases that may worsen when receiving systemic steroid therapy or any other form of immunosuppressive therapy (except for patients with type I diabetes, vitiligo, psoriasis or hypothyroidism or hyperthyroidism that do not require immunosuppressive therapy).
• Immunosuppressive drugs are used, except for the following cases: intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injections), physiological doses of systemic corticosteroids (≤ 10 mg / day prednisone or equivalent dose), steroid pre medication for hypersensitivity reactions (e.g., CT scan pre medication).
• Major surgery was performed within 4 weeks before enrollment, and / or there were unhealed wounds, ulcers or fractures.

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead

Study Sites (1)

Sichuan Cancer Hospital

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Neoplasm Metastasis

Interventions

Immune Checkpoint Inhibitors; Chemoradiotherapy

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: August 28, 2022
• First Posted: August 30, 2022
• Study Start: August 1, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

CN (1)