Recurrent or Metastatic Nasopharyngeal Carcinoma
Conditions
Keywords
Nasopharyngeal Carcinoma, Recurrent, Metastatic, Mitoxantrone Hydrochloride Liposome, PD-1 Blockade
Brief summary
This is a prospective, single-arm Phase 2 study to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection combined with PD-1 blockade in patients with recurrent (not unable to locally curative treatment) or metastatic NPC who failed at least first-line platinum-containing standard regimen and/or anti PD-1/L1.
Detailed description
Thirty-two recurrent (not unable to locally curative treatment) or metastatic NPC patients who had failed at least first-line platinum-containing standard regimen and/or anti PD-1/L1 were eligible to receive mitoxantrone hydrochloride liposome injection combined with PD-1 blockade once every 3 weeks for up to 8 cycles, following PD-1 blockade alone once every 3 weeks for 2 years. All patients will be treated until disease progression as determined by the investigator based on RECIST 1.1 criteria, intolerable toxicity, subject withdrawal of informed consent, initiation of new antitumor therapy, loss of follow-up, death, or study completion, whichever occurs first. Regular visits and imaging examinations will be conducted to evaluate the efficacy and safety of the treatment regimen.
Interventions
Mitoxantrone hydrochloride liposome injection once every 3 weeks for up to 8 cycles or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.
DRUGPD-1 Inhibitors
PD-1 blockade (comprising tislelizumab \<200 mg/cycle\>, carrellimab \<200 mg/cycle\>, or toripalimab \<240 mg/cycle\>) once every 3 weeks for two years, or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.
Sponsors
Ming-Yuan Chen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Willing to participate in the study, sign the informed consent form (ICF), and comply with study plan visits, treatment plans, laboratory tests, and other study procedures. 2. Nasopharyngeal carcinoma confirmed by histopathology (differentiated or undifferentiated non-keratinous carcinoma). 3. Age ≥ 18 & ≤ 70 years. 4. PS (Performance Status) score 0-1. 5. Recurrent or metastatic nasopharyngeal carcinoma that has failed first-line platinum-containing standard regimen and/or second-line standard regimen failure. 6. Previously received at least one line of systemic therapy. (Progression after radical concurrent chemoradiotherapy, during neoadjuvant or adjuvant therapy, or within 6 months after the end of treatment can be recorded as 1-line therapy). 7. Recurrent or metastatic nasopharyngeal carcinoma that has failed anti PD-1/L1: anti PD-1/L1 exposure at least 6 weeks, and the protocol used at the time of enrollment in this study meets one of the following two points: (1) Relapse during adjuvant therapy after radiotherapy, or relapse within 6 months after the end of treatment; (2) First-line treatment phase, progression during anti PD-1/L1 treatment, or progression within 3 months after the end of anti PD-1/L1 (whether combined with chemotherapy/targeting drugs); 8. At least one measurable lesion according to RECIST 1.1 criteria (the spiral CT scan diameter of the measurable lesion is ≥ 10 mm or the short diameter of the enlarged lymph node is ≥15mm ); lesions that have undergone local treatment can be selected as target lesions if there is clear evidence of significant progress compared to the end of treatment. 9. All acute toxicities of previous antitumor therapy have returned to ≤ grade 1 (according to NCI-CTCAE v5.0) or reached the level specified in the inclusion/
Exclusion criteria
. (Except for partial toxicity, such as alopecia, hair color change, nail change, fatigue, etc., which do not pose safety risks to subjects). 10. Adequate main organ function. a. Hematology: neutrophil absolute value (ANC) ≥1.5×10\^9/L, hemoglobin (Hb) ≥ 9.0 g/dL, platelets ≥ 100×10\^9/L; b. Liver function: bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert disease and serum bilirubin level ≤ 3 times ULN could be enrolled; patients with liver metastasis, ≤ 5 times ULN), AST and ALT ≤ 3 times ULN, and alkaline phosphatase ≤ 3 times ULN; Albumin ≥ 3 g/dL; c. International Normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 times; d. Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min according to Cockcroft-Gault formula; e. Proteinuria: urinary protein/creatinine ratio (UPC ratio) \< 1.0. If the UPC ratio is less than or equal to 0.5, no further check is required. Patients with UPC ratio \> 0.5 and those with 24-hour urinary protein \< 1000 mg could be enrolled; f. Note: The UPC ratio of random urine is a quantitative estimate of 24-hour urinary protein, and the two have a good correlation. UPC ratio can be calculated using the following formula: (a) Urinary protein/urinary creatinine (if both protein and creatinine are mg/dL); (b) (urinary protein)\*0.088/ urinary creatinine (if urinary creatinine is mmol/L). 11. Survival is expected to be ≥ 3 months. 12. Female subjects with negative blood human chorionic gonadotropin (HCG) (except for menopause and hysterectomy), female subjects of reproductive age and their partners using effective contraception during the trial period and within 6 months after the end of the last dose (e.g. Combined hormones \[containing estrogen and progesterone combined to inhibit ovulation, progesterone contraception combined to inhibit ovulation, IUD, intrauterine hormone release system, bilateral tubal ligation, vasectomy, abstinence from sex, etc.). 13. Male patients and their partners agree to use one of the contraceptive measures described in Article 9.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Through study completion, an average of 2 years | Objective response rate (ORR) is defined as the proportion of patients with a complete response or partial response to treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Through study completion, an average of 2 years | Duration of Response (DOR) is defined as time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death |
| Disease control rate (DCR) | Through study completion, an average of 2 years | Disease Control Rate (DCR) is defined as the percentage of patients who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents |
| Progression-free survival (PFS) | Through study completion, an average of 2 years | Progression-Free Survival PFS is defined as the time from randomization to progression or death |
| Overall survival (OS) | Through study completion, an average of 2 years | Overall survival (OS) is defined as the duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death. |
Countries
China
Contacts
Primary ContactMingyuan Chen, Doctor
Backup ContactJijin Yao, Doctor
Outcome results
None listed