Clinical trial NCT05222035: PD-1 Inhibitor Plus G-CSF in Recurrent/Metastatic NPC With First-line Treatment Failure
Official title: Camrelizumab Plus PEG-rhG-CSF in Recurrent/Metastatic NPC With First-line Treatment Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: PD-1 Inhibitor
G-CSF
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-02-03
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recurrence and metastasis are the main causes of treatment failure of NPC. Preliminary clinical studies have found that the overall response rate of PD-1 inhibitors in treating ≥2 line R/M NPC is about 25%.

Recent studies have shown that G-CSF can significantly increase the proportion of effector cells dominated by CD4+ T cells, improve the diversity of peripheral blood TCR, and regulate the immune status of patients. Therefore, we suspect that G-CSF may have a synergistic effect on PD-1 inhibitor, thus enhance the efficacy of PD-1 inhibitor monotherapy.


Eligibility criteria: Inclusion Criteria:

1. Male or female; 18-75 years of age.
2. Received one or more lines of therapy, which must include prior treatment with a platinum agent (except for patients who are unfit or refuse platinum-containing regimens) and must not be amenable to potentially curative radiotherapy or surgery. \[Received neoadjuvant/adjuvant/concurrent platinum-containing regimen for radical therapy (radiotherapy or surgery), with recurrence ≤6 months following completion of therapy can be recognized as one line\]
3. Subjects diagnosed with pathological confirmed non-keratinizing (WHO-II/III) metastatic NPC, or subjects with recurrent NPC that is unfit for local treatment
4. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
5. ECOG performance status of 0 or 1.
6. Have recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to any anti-tumor therapy 4 weeks earlier. Except for hair loss, hair color change, nail change, fatigue, etc., which do not pose safety risks to subjects.
7. Life expectancy more than 12 weeks.
8. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by:

   Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; INR, APTT≤1.5 x ULN.
9. Female subjects agree not to be pregnant or lactating from beginning of the study screening through at least 3 months after receiving the last dose of study treatment. Both men and women of reproductive potential must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy.
10. Be willing and able to provide written informed consent/assent for the trial.

Exclusion Criteria:

1. Subjects who underwent anti-PD-1 /PD-L antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway).
2. Known history of hypersensitivity to any components of the Camrelizumab and PEG-rhG -CSF formulation or other monoclonal antibodies.
3. Prior chemotherapy, targeted small molecule therapy, or radical therapy within 2 weeks prior to Study Day 1
4. Diagnosed and/or treated additional malignancy within 5 years of enrollment, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast carcinoma.
5. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
6. Active central nervous system metastases and/or carcinomatous meningitis
7. Severe, uncontrolled angiocardiopathy (heart failure \> class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.).
8. History of non-infectious pneumonitis that required steroids or current pneumonitis
9. Active infection requiring systemic therapy
10. Be known to have active tuberculosis.
11. Human immunodeficiency virus (HIV) positive
12. Hepatitis B or C positive
13. Live vaccine within 30 days of planned start of study drug
14. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Primary outcomes:
measure: Objective response rate
timeFrame: 1 year
Secondary outcomes:
measure: The proportion of patients who achieved disease control
timeFrame: 1 year
measure: The proportion of patients who achieved clinical benefit
timeFrame: 1 year
measure: median progression-free survival
timeFrame: 1 year
measure: Duration of response
timeFrame: 1 year
measure: Adverse events
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: