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About
This phase II trial tests how well enfortumab vedotin works for treating patients with squamous cell carcinoma of the penis that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them.
Full description
PRIMARY OBJECTIVE:
I. To estimate the best response rate of enfortumab vedotin treatment for patients with metastatic penile squamous cell carcinoma (mPSCC).
SECONDARY OBJECTIVES:
I. To determine overall response rate (ORR). II. To determine safety and tolerance of enfortumab vedotin in men with mPSCC. III. To characterize duration of response to enfortumab vedotin in mPSCC. IV. To estimate median overall survival and progression-free survival in men with mPSCC treated with enfortumab vedotin.
V. To analyze response in subgroups by human papillomavirus (HPV) status (related/unrelated as assessed by p16 biomarker).
OUTLINE:
Patients receive enfortumab vedotin intravenously (IV) over 30 minutes on days 1,8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months until progressive disease, followed by every 6 months for up to 5 years from registration.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age ≥ 18 years
Histological confirmation of squamous cell carcinoma of the penis (PSCC): NOTE: Biopsy confirmation of at least one site of metastasis is encouraged but not required.
At least one site of metastatic or unresectable PSCC. NOTE: Prior therapy is not required for patients whose treatment is considered palliative (for example, presence of distant metastasis). NOTE: Patients who are potentially curable (any T, N1 - N3, M0) must have had tumor progression after standard chemotherapy, radiotherapy, or surgery, or be unable to receive such treatment. Eligible stages include:
Patients with clinical N1, M0 mPSCC at protocol entry must be ineligible for surgery because of comorbidities or clinical T4 disease, or have refused surgery
Patients with clinical N1 - N3, M0, and no prior systemic therapy must be:
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Prior therapy is allowed. Patients may be treatment-naïve or have had any number of prior anti-cancer treatments
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Hemoglobin ≥ 9.0 g/dL obtained ≤15 days prior to registration
Absolute neutrophil count (ANC) ≥ 1000/mm^3 obtained ≤ 15 days prior to registration
Platelet count ≥ 100,000/mm^3 obtained ≤ 15 days prior to registration
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with Gilbert's disease obtained ≤ 15 days prior to registration
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN obtained ≤ 15 days prior to registration
Glomerular filtration rate (GFR) or calculated creatinine clearance ≥ 30 ml/min as estimated using the Cockcroft-Gault formula or as measured by 24-hour urine collection obtained ≤ 15 days prior to registration
Provide written informed consent
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
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:
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
Failure to recover from any of the following therapies prior to registration:
Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
Uncontrolled intercurrent illness including, but not limited to:
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] ribonucleic acid (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
Primary purpose
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Interventional model
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28 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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