Safety Evaluation of Alluminox and Pembrolizumab Sequential Therapy in Primary Squamous Cell Carcinoma of the Nasopharynx and Nasal/Sinus Cavities

JRCT ID: jRCTs031230728

Registered date:22/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: nasopharyngeal carcinoma, nasal cavity/paranasal sinuses squamous cell carcinoma
• Date of first enrollment: 22/03/2024
• Target sample size: 12
• Study type: Interventional
• Intervention(s): Alluminox and pembrolizumab sequential therapy

Outcome(s)

• Primary Outcome: DLT (dose limiting toxicity) rate
• Secondary Outcome: The response rate for metastatic lesion except for local lesion, disease control rate, progression free survival, overall survival, and adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Diagnosis of nasopharyngeal carcinoma (squamous cell carcinoma or lymphoepithelial carcinoma) of WHO Classification Type I/II/III or squamous cell carcinoma of the nasal cavity/paranasal sinuses by histological examination.
2) Diagnosed with distant metastasis or recurrence at enrollment and not eligible for curative treatment. Patients who are eligible for salvage surgery but refuse to undergo surgery are also eligible.
3) Patients have locally recurrent disease after radiotherapy that can be treated with head and neck alluminox via a nasal approach.
4) Patients have not been previously treated with anti-PD-1/PD-L1 antibodies (including treatment for other diseases).
5) In addition to locally recurrent disease, the patient has lymph node involvement with a short diameter of at least 15 mm or non-lymph node involvement with a long diameter of at least 10 mm.
6) Patients must be 16 or older at the time of enrollment.
7) Performance status (ECOG) of 0-1.
8) The latest laboratory values within 14 days prior to enrollment (the same day of the week two weeks prior to enrollment is acceptable) meet all of the following.
a) Neutrophil count: 1200 /mm3 or more
b) Platelet count: 10x104 /mm3 or more
c) Hemoglobin: 9.0 g/dL or more (No blood transfusion within 14 days prior to the date of blood collection for the test used for registration)
d) Total bilirubin: 1.5 mg/dL or less
e) AST (GOT): 100 IU/L or less
f) ALT (GPT): 100 IU/L or less
g) Serum creatinine: 1.5 mg/dL or less
9) In women of childbearing potential, the patient agrees to use contraception from the date of consent until seven months after the last dose of cetuximab sarotalocan sodium or five months after the last dose of pembrolizumab, whichever is later. For
men, consent to contraception from the time consent is obtained until seven months after the last dose of cetuximab sarotarocan sodium or seven months after the last dose of pembrolizumab, whichever is later.
10) Written consent to participate in the trial has been obtained from the patient. If the patient is a minor when obtaining consent, permission has also been obtained from a surrogate (parent or legal guardian).

Exclude criteria

1) Patients with active overlapping cancers (simultaneous overlapping/multiple cancers and iatrogenic overlapping/multiple cancers with a disease-free interval of 5 years or less. However, even if the disease-free period is less than five years, a history
of cancer equivalent to a 5-year relative survival rate of 95% or more, such as stage I prostate cancer, stage 0 or stage I laryngeal cancer with complete response to radiotherapy, and completely resected cancer with the following pathological stages, is
not included in active multiple/several cancers).Gastric cancer (adenocarcinoma, general type): stage 0-I; Colon cancer (adenocarcinoma): stage 0-I; Rectal cancer (adenocarcinoma): stage 0-I; Esophageal cancer (squamous cell carcinoma, adenosquamous carcinoma, basaloid cell carcinoma): stage 0; Breast cancer (noninvasive ductal carcinoma of breast, noninvasive lobular carcinoma): stage 0; Breast cancer (invasive ductal carcinoma of breast, invasive lobular carcinoma, Paget's disease): stage 0-IIA Uterine cancer (endometrial adenocarcinoma, mucinous adenocarcinoma): stage I, prostate cancer (adenocarcinoma): stage I-II, cervical cancer (squamous cell carcinoma): stage 0, thyroid cancer (papillary carcinoma, follicular carcinoma): stage I, II, III, renal cancer (clear cell carcinoma, pigment cell carcinoma): stage I, other lesions equivalent to intramucosal cancerIn principle, staging is based on the UICC-TNM 8th edition or equivalent.
2) Active infection requiring systemic treatment (fever of 38.0 deg C or higher, and bacterial infection proven by diagnostic imaging or bacteriological examination. Local infections that do not affect the general condition are excluded).
3) HBs antigen positive, HCV-RNA positive, HIV antibody positive, or HTLV-1 antibody positive (HIV and HTLV-1 antibodies may be untested for registration).
4) HBs antigen negative, HBs or HBc antibody positive, and HBV-DNA quantification positive (registration is acceptable if detection sensitivity is below detection sensitivity).
5) Pregnant, possibly pregnant, or lactating.
6) Psychosis or psychiatric symptoms that would preclude participation in the study.
7) Requires continued use of anticoagulants or antiplatelet agents (temporary discontinuation is not possible).
8) Has a history of an iodine allergy.
9) Has a concomitant severe hypersensitivity reaction to antibody products or a history of such reaction.
10) Active autoimmune disease requiring systemic treatment (disease-modifying drugs, corticosteroids, or immunosuppressive agents) within the past two years. However, replacement therapy (e.g., thyroxine, insulin, or corticosteroid replacement therapy at physiologic doses (prednisolone equivalent: 10 mg/day or less) for adrenal or pituitary insufficiency) is not considered this systemic treatment and may be used.
11) Complicated interstitial disease/pulmonary inflammation or a history of (non-infectious) interstitial pneumonia/pulmonary inflammation requiring steroid administration
12) Complicated with poorly controlled hypertension/diabetes mellitus.
13) Complicated with unstable angina pectoris (angina that occurred within the last three weeks or with worsening attacks). Or a history of myocardial infarction within the last six months.
14) Diverticulitis or symptomatic peptic ulcer.
15) Previous transplantation therapy, such as hematopoietic stem cell transplantation.
16) Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4, or other Tcell regulating antibody therapy or cancer vaccine.
17) Received or will receive a live vaccine or attenuated vaccination within 28 days before the first dose of pembrolizumab.
18) Other patients deemed by the physician to be unsuitable for the safe conduct of this study.

Related Information

• Primary Sponsor: Honma Yoshitaka
• Secondary Sponsor: Rakuten Medical K.K.