Pembrolizumab in Combination with Flutamide Treatment for Recurrence / Metastasis HNSCC

NCT06694350 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: KF20240822
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a single center, single arm clinical trial for newly diagnosed patients with locally advanced head and neck squamous cell carcinoma. The main purpose is to evaluate the efficacy and safety of flutamide combined with standard immunotherapy for advanced / recurrent head and neck squamous cell carcinoma. In our previous study, we found that AR can affect the occurrence and development of tumors by regulating the differentiation of cd8+t cells. We used three different castration drugs (flutamide, goserelin and abiraterone) in animal models to treat primary and tumor bearing head and neck squamous cell carcinoma mice respectively, and found that castration treatment could significantly inhibit the tumor growth of head and neck squamous cell carcinoma. In addition, in animal models, we compared the efficacy of the combination of castration therapy and low-dose cisplatin with that of the existing first-line chemotherapy drug cisplatin, and found that the combination of castration therapy and low-dose cisplatin can significantly improve the treatment effect of head and neck squamous cell carcinoma and reduce the adverse reactions brought by the drug. Therefore, we infer that flutamide combined with standard immunotherapy can fully inhibit the growth of HNSCC and improve the prognosis of HNSCC patients.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC

Outcome Measures

Primary Outcomes (1)

• PFS

  The Progression-Free-Survival of Interventions group

  Up to 4 years

Secondary Outcomes (3)

• ORR

  Up to 4 years

• DOR

  Up to 4 years

• OS

  Up to 4 years

Study Arms (1)

Pembrolizumab+Flutamide

EXPERIMENTAL

Pembrolizumab 200mg ivgtt once +Flutamide 250mg，Q8h

Drug: Pembrolizumab+Flutamide

Interventions

Pembrolizumab+Flutamide DRUG

Pembrolizumab 200mg ivgtt once +Flutamide 250mg，Q8h

Pembrolizumab+Flutamide

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old, ≤ 85 years old
• Histologically or cytologically proven squamous cell carcinoma of the head and neck; Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx
• Measurable primary lesions per RECIST 1.1 criteria
• Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions)
• ECOG performance status of 0 or 1
• Unresectable primary, recurrent, and / or metastatic HNSCC
• No active autoimmune disease
• No concurrent malignancy
• Life expectancy is estimated to be over 3 months
• Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO)
• No abvious signs of hematological disorders, ANC≥1.5×109 /L, platelets ≥100×109 /L, Hb≥ 90 g/L,WBC ≥3.0×109 /L before enrollment, no blood transfusion and bleeding tendency within 7 days
• ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin ≤ 3 x ULN
• Serum creatinine ≤1.5 or creatinine clearance\>50 mL/min
• HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays
• Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent

You may not qualify if:

• Patients who are suitable for local treatment and have the intention of local treatment
• Received systemic treatment with Chinese patent drugs with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin) within 2 weeks before the first administration
• Patients with tumor progression after previous treatment with flutamide analogues (antiandrogens)
• Other malignant tumors occurred within 5 years or suffered from at the same time in the current period, except for cured non melanoma skin cancer or other tumors / cancers that have undergone radical treatment and have no signs of disease for at least 5 years;
• According to the criteria of common adverse event terminology (NCI ctcaev5.0), there was peripheral neuropathy ≥ grade 2
• With known active central nervous system metastasis (CNS) and / or cancerous meningitis
• Subjects who did not recover from any acute effects of previous surgery, chemotherapy or radiotherapy, i.e. did not fall to grade ≤ 1 (NCI ctcaev5.0) (excluding hair loss). Chronic late toxicity from previous radiotherapy and / or surgery is allowed if nutritional status is stable
• Any component of the study drug or preparation has led to severe allergic reactions, including known severe allergic reactions to flutamide and (NCI ctcaev5.0 ≥ grade 3)
• Have received anti-tumor drug treatment (such as chemotherapy, hormone therapy, immunotherapy, antibody therapy, radiotherapy, etc.) within 4 weeks or 4 weeks before the first administration, except for palliative radiotherapy for bone to reduce pain
• Major surgery within 4 weeks before the first dose or expected during this study
• Immunosuppressive drugs were required 2 weeks or within 2 weeks before the first dose or during the study
• Subjects who are known to have active, or have a history of autoimmune disease that may recur
• Subjects with known history of interstitial lung disease, non infectious pneumonia, or high suspicion of interstitial lung disease
• Hepatitis B or C virological examination meets any of the following requirements at the time of screening:
• HBsAg is positive, and the titer of hepatitis B virus deoxyribonucleic acid (HBV DNA) in peripheral blood is ≥ 104 copies /ml or ≥ 2000 iu/ml;

Sponsors & Collaborators

• Zhejiang Provincial People's Hospital: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Central Study Contacts

Ge Minghua, Doctor

CONTACT

+86 13605813782; gemingh@163.com

Study Design

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

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 19, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 19, 2024

Record last verified: 2024-11