Ensayos clínicos

Inclusion Criteria:

• Male, aged 18 years or older on the day of consent.
• Histologically-proven squamous cell carcinoma of the penis.
• Stage:
  • any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or;
  • any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0 or;
  • any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy) M0;
  • any T, any N, M1.
• Measurable disease as determined by RECIST (version 1.1) criteria.
• Patients may have received any number of prior anti-cancer treatments or be treatment naïve.
• Performance Status ECOG 0, 1 or 2.
• Required laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.0/mcL
• Platelet count ≥ 100/mcL
• Hemoglobin ≥ 9 g/dL (transfusion of PRBCs allowed).
• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease.
• Creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Written informed consent.

Exclusion Criteria:

• Pure verrucous carcinoma of the penis.
• Non-squamous malignancy of the penis.
• Squamous carcinoma of the urethra.
• Preexisting sensory or motor neuropathy ≥ Grade 2.
• Active central nervous system (CNS) metastases.
  • Exception: Treated CNS metastases are allowed if all of the following are true:
  • CNS metastases are clinically stable for ≥ 6 weeks prior to registration;
  • If needed, steroid dose is stable and ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks prior to registration;
  • Baseline imaging shows no evidence of new or enlarged brain metastasis;
  • No leptomeningeal disease.
• History of uncontrolled diabetes mellitus ≤ 3 months prior to registration.
  • NOTE: Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8.0% or HbA1c 7.0-7.9% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Any of the following prior therapies:
  • Major surgery ≤ 4 weeks prior to registration;
  • Radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy ≤ 2 weeks prior to registration.
• Immunocompromised patients and patients known to be HIV positive.
• Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection requiring systemic treatment;
  • history of cerebral vascular event (stroke or transient ischemic attack);
  • myocardial infarction or symptomatic congestive heart failure (NYHA Class III-IV) ≤ 6 months prior to registration;
  • unstable angina pectoris;
  • cardiac arrhythmia; or
  • psychiatric illness/social situations that would limit compliance with study requirements (e.g., history of substance abuse).
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection.
  • NOTE: Routine antimicrobial prophylaxis is allowed.
• Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected).
• Known active keratitis or corneal ulcerations.
  • NOTE: Superficial punctate keratitis is allowed if the disorder is being adequately treated.
• Known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) OR subject has known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells.
• Other active malignancy ≤ 2 years prior to registration.
  • EXCEPTIONS: Locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ of the breast or low risk Gleason 6 prostate cancer.
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile).
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Chemotherapy-naïve patients who are potentially curable (any T, N1 – N3, M0) in the absence of any condition that precludes cisplatin-based chemotherapy, such as low GFR, peripheral neuropathy, hearing impairment, or psychosocial considerations.