Trial Title:
Clinical Study of Mitoxantrone Hydrochloride Liposome Combined With PD-1 Blockade in Recurrent or Metastatic NPC
NCT ID:
NCT06472713
Condition:
Recurrent or Metastatic Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Recurrence
Mitoxantrone
Conditions: Keywords:
Nasopharyngeal Carcinoma
Recurrent
Metastatic
Mitoxantrone Hydrochloride Liposome
PD-1 Blockade
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome injection
Description:
mitoxantrone hydrochloride liposome injection combined with PD-1 blockade once every 3
weeks for up to 8 cycles, following the uniform PD-1 blockade alone once every 3 weeks
for two years, or until intolerable toxicity, subject withdrawal of informed consent,
initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.
Arm group label:
Mitoxantrone group
Other name:
PD-1 blockade
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.
Criteria for eligibility:
Criteria:
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.
Exclusion Criteria:
1. Recurrent lesions in local areas suitable for radical method (surgery) treatment.
2. Severe allergy to mitoxantrone or liposome (such as systemic rash/erythema
hypotension, bronchospasm, angioedema, or anaphylaxis).
3. Prior treatment with doxorubicin or other anthracyclines and the cumulative
doxorubicin doses greater than 350 mg/m^2 (anthracycline equivalent: 1 mg
doxorubicin = 2 mg epirubicin = 2 mg daunorubicin = 0.5 mg normethoxydaunorubicin =
0.45 mg mitoxantrone).
4. Estimated survival < 3 months.
5. Diagnosed and/or treated with other malignancies within 5 years prior to initial
administration. (except for cervical cancer, skin basal cell or squamous cell
carcinoma, localized prostate cancer, and ductal carcinoma in situ after radical
treatment).
6. Received surgery, chemotherapy, radiotherapy, immunotherapy, or any investigational
drug or other antitumor therapy within the 4 weeks prior to initial administration
(less than 2 weeks after palliative radiotherapy).
7. Patients with hypertension who cannot be reduced to the normal range by
antihypertensive drugs (systolic blood pressure > 140 mmHg/ diastolic blood pressure
> 90 mmHg); Have ≥ grade II coronary heart disease; Any of the following conditions
occurred during the first 6 months of enrollment: Myocardial infarction,
severe/unstable angina pectoris, NYHAII grade or higher cardiac insufficiency, grade
2 or higher persistent arrhythmias (including prolonged QTc interval > 450ms in
men), Women > 470ms), any grade of atrial fibrillation, coronary/peripheral artery
bypass grafting, symptomatic congestive heart failure, or cerebrovascular accident
(including transient ischemic attack or symptomatic pulmonary embolism); The
ejection fraction of the heart is below 50% or below the lower limit of the range of
laboratory tests at the study center. Patients with a history of arterial
thromboembolism events and venous thromboembolism > grade 3. (Patients with S-T
elevation ≥ 2mm on the ECG may be enrolled if they do not show signs of recent
myocardial infarction or ischemia) (according to NCI-CTCAE v5.0).
8. Severe infection (such as intravenous antibiotics, antifungals, or antivirals as
required by clinical practice) during the 4 weeks prior to the first dose, or any
unexplained fever >38.5 ° C during the screening period / 7 days prior to the first
dose, or white blood cell count >15×109/L at baseline.
9. Immunosuppressants, or systemic hormone therapy (dose >10mg/ day of prednisone or
other therapeutic hormone) are being used for the purpose and continue to be used
within 2 weeks before the first dose.
10. The subject has any active autoimmune disease or history of autoimmune disease
(including but not limited to: interstitial pneumonia, uveitis, enteritis,
hepatitis, pituitaritis, nephritis, hyperthyroidism, hypothyroidism; Patients with
vitiligo or who had complete remission of asthma in childhood and did not require
any intervention as adults were included; Patients with asthma requiring medical
intervention with bronchodilators were not included).
11. Exacerbations of COPD or other respiratory diseases requiring hospitalization within
1 month prior to registration.Patients with active tuberculosis (TB) who are
receiving anti-TB therapy or have received anti-TB therapy within 1 year prior to
screening.
12. HIV-positive people; HBsAg positive and HBV DNA copy number positive (quantitative
detection ≥1000 cps/ml); Chronic hepatitis C blood screening positive (HCV antibody
positive).
13. Live vaccine was administered within 4 weeks before the first dose or possibly
during the study period.
14. Pregnant or lactating women.
15. Women with reproductive potential and sexually active men who are unwilling/unable
to use medically acceptable forms of contraception.
16. Have any serious and/or uncontrollable medical conditions that, as determined by the
investigator, may affect the patient's participation in the study, such as
alcoholism, drug abuse, other serious diseases (including mental illness) that
require combined treatment, serious laboratory abnormalities, and family or social
factors that affect the safety of the patient.
17. Other situations that the investigator determines to be inappropriate for
participation.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
July 1, 2024
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Ming-Yuan Chen
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06472713
