Clinical trial NCT05147844: Toripalimab Combined With Radiotherapy in the Treatment of Oligometastatic Nasopharyngeal Carcinoma
Official title: Antitumor Activity of Toripalimab Combined With Radiotherapy in the Treatment of Oligometastatic Nasopharyngeal Carcinoma: A Single-arm, Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: Southwest Hospital, China
name: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
name: Chongqing University Cancer Hospital
First posted: 2021-12-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study was to determine the efficacy and safety of toripalimab combined with radiotherapy in the treatment of oligometastatic nasopharyngeal carcinoma

Detailed description: Chemotherapy has been widely used for the treatment of relapsed or metastatic nasopharyngeal carcinoma. However, the long-term survival and quality of life of patients was still unsatisfactory. In this prospective, multicenter, single arm study, the efficacy and safety of toripalimab combined with radiotherapy in the treatment of oligometastatic nasopharyngeal carcinoma is determined.

Eligibility criteria: Inclusion Criteria:

1. Must have signed written informed consent and able to comply with study procedure
2. 18-75 years old
3. Histologically or cytologically confirmed nasopharyngeal carcinoma
4. Pathology or imaging confirmed metastatic nasopharyngeal carcinoma.( Clinical stage of IVB according to the 8th edition of AJCC)
5. Imaging (preferred PET-CT) confirmed oligometastatic NPC (defined as ≤5 metastatic lesions, ≤2 metastatic organs)
6. Have not received any treatment for metastatic nasopharyngeal carcinoma.
7. Unsuitable or unwilling to receive chemotherapy according to the judgment of investigator.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-1
9. Estimated life ≥ 6 month
10. At least 1 measurable lesions according to RECIST v1.1
11. Adequate organ function, defined as achieving the following laboratory test results within 7 days before enrollment: ANC≥1.5×10\^9/L，PLT≥100×10\^9/L，Hb≥90g/L((Have not accepted blood transfusion or growth factors within 14 days)；the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; activated partial thromboplastin time(APTT) ≤1.5 × ULN；serum creatinine≤1.5×ULN or estimated glomerular filtration rate(GFR) ≥ 60 mL/min/1.73 m2; total bilirubin≤1.5×ULN（total bilirubin\<3×ULN for patients with Gilbert syndrome）; AST and ALT ≤ 2.5×ULN (AST and ALT ≤ 2.5×ULN for patients with liver metastasis);

Exclusion Criteria:

1. Allergy to any component of toripalimab
2. With any active autoimmune disease or a history of autoimmune disease that may relapse

   Note: Patients with the following diseases were not excluded and should be further screened:

   Controlled type 1 diabetes; Hypothyroidism (could be controlled just by hormone replacement therapy); Controlled celiac disease; Skin diseases that do not require systemic treatment (e.g. vitiligo, psoriasis, alopecia); Any other disease which is not expected to be relapsed without external stimulate
3. Any active malignancy ≤ 2 years before randomization except for the specific cancer under investigation in this study and any locally relapsed cancer that has been cured after treatment (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
4. Received corticosteroid therapy at a dose ≥ 10 mg prednisone per day or any other systemic immunosuppressive therapy within 14 days prior to enrollment.
5. Patient with uncontrolled diabetes, or abnormal potassium, sodium or corrected calcium levels (≥ grade 1) after receiving standard treatment, or ≥ grade 3 hypoalbuminemia within 14 days prior to enrollment
6. Patient with a history of interstitial lung disease, non-infectious pneumonia or uncontrollable diseases, including pulmonary fibrosis, acute lung disease, hypertension, etc.
7. Evidence of severe chronic or active infections (including tuberculosis infection) requiring systemic antibiotics, antibacterial or antiviral therapy within 14 days prior to enrollment
8. Patient with a history of HIV infection
9. Evidence of contraindications of immunotherapy or radiotherapy
10. Patient with untreated chronic hepatitis B or HBV-DNA≥ 500 IU/mL, or active hepatitis C.

    Note: Patients with inactive infection of hepatitis B surface antigen (HBsAg), stable hepatitis B after treatment (HBV DNA \< 500 IU/mL）and cured hepatitis C could be included.
11. Have undergone any operation requiring general anesthesia within 28 days prior to enrollment
12. Previous allogeneic stem cell transplantation or organ transplantation
13. Patient with any of the following cardiovascular risk factors: Cardiogenic chest pain within 28 days prior to enrollment, which is defined as moderate pain that limits instrumental activities of daily life; Symptomatic pulmonary embolism within 28 days prior to enrollment; Acute myocardial infarction within 6 months prior to enrollment; Grade III or IV disease according to the New York Heart Association within 6 months prior to enrollment;≥ Grade 2 ventricular arrhythmias within 6 months prior to enrollment or the first administration; With a history of cerebrovascular accident within 6 months prior to enrollment or the first administration
14. Grade 2 peripheral nerve disease according to NCI-CTCAE V5.0
15. Underlying medical conditions (including abnormal laboratory test values) that: affect drug administration; affect the interpretation of toxicity or AE; lead to poor compliance; alcohol or drug abuse or dependence
16. Participate in another interventional clinical study at the same time

Primary outcomes:
measure: 1-year progression-free survival rate according to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. 1 year
Secondary outcomes:
measure: PFS according to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: OS
timeFrame: up to 5 years
measure: 2-year progression-free survival rate according to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: 2-year overall survival
timeFrame: From date of randomization until death, loss to follow-up, or study termination by the Sponsor whichever occurs first.Up to 3.5 approximately years
measure: 1-year progression-free survival rate according to irRECIST
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 1 approximately year
measure: ORR according to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: DCR according to RECIST v1.1
timeFrame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
measure: DoR according to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: AE(SAE)
timeFrame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Xinqiao Hospital of Chongqing
state: Chongqing
city: Chongqing
country: China
facility: the second affiliated hospital of Army medical university
state: Chongqing
Study officials:
References: