Clinical Study of Mitoxantrone Hydrochloride Liposome Combined with PD-1 Blockade in Recurrent or Metastatic NPC

NCT06472713 | Recruiting Phase 2 DMC

• 1 other identifier: ZDWY.BYAFZZX.027
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent or Metastatic Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; Recurrent; Metastatic; Mitoxantrone Hydrochloride Liposome; PD-1 Blockade

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR) is defined as the proportion of patients with a complete response or partial response to treatment

  Through study completion, an average of 2 years

Secondary Outcomes (4)

• Duration of Response (DOR)

  Through study completion, an average of 2 years

• Disease control rate (DCR)

  Through study completion, an average of 2 years

• Progression-free survival (PFS)

  Through study completion, an average of 2 years

• Overall survival (OS)

  Through study completion, an average of 2 years

Study Arms (1)

Mitoxantrone group

EXPERIMENTAL

Mitoxantrone hydrochloride liposome (30 mg/cycle) injection combined with PD-1 blockade (comprising tislelizumab \<200 mg/cycle\>, carrellimab \<200 mg/cycle\>, or toripalimab \<240 mg/cycle\>) 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.

Drug: Mitoxantrone hydrochloride liposome injection; Drug: PD-1 Inhibitors

Interventions

Mitoxantrone hydrochloride liposome injection DRUG

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.

Mitoxantrone group

PD-1 Inhibitors DRUG

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.

Mitoxantrone group

Eligibility Criteria

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

You may qualify if:

• 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.
• Nasopharyngeal carcinoma confirmed by histopathology (differentiated or undifferentiated non-keratinous carcinoma).
• Age ≥ 18 \& ≤ 70 years.
• PS (Performance Status) score 0-1.
• Recurrent or metastatic nasopharyngeal carcinoma that has failed first-line platinum-containing standard regimen and/or second-line standard regimen failure.
• 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).
• 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);
• 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.

You may not qualify if:

• 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).
• Survival is expected to be ≥ 3 months.
• 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.).
• Male patients and their partners agree to use one of the contraceptive measures described in Article 9.
• Recurrent lesions in local areas suitable for radical method (surgery) treatment.
• Severe allergy to mitoxantrone or liposome (such as systemic rash/erythema hypotension, bronchospasm, angioedema, or anaphylaxis).
• 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).
• Estimated survival \< 3 months.
• 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).
• 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).
• 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).
• 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.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Ming-Yuan Chen: lead

Study Sites (1)

The Fifth Affiliated Hospital, Sun Yat-sen University

Zhuhai, Guangdong, 519000, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Nasopharyngeal Carcinoma; Neoplasm Metastasis

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Mingyuan Chen, Doctor

CONTACT

18124188280; chmingy@mail.sysu.edu.cn

Jijin Yao, Doctor

CONTACT

15692424219; yaojj23@mail.sysu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: June 15, 2024
• First Posted: June 25, 2024
• Study Start: July 20, 2024
• Primary Completion: October 31, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: January 13, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)