Trial Title:
Enfortumab Vedotin for the Treatment of Patients With Metastatic or Unresectable Squamous Cell Carcinoma of the Penis
NCT ID:
NCT06104618
Condition:
Metastatic Penile Squamous Cell Carcinoma
Stage III Penile Cancer AJCC v8
Stage IV Penile Cancer AJCC v8
Unresectable Penile Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Penile Neoplasms
Immunoconjugates
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Enfortumab Vedotin
Description:
Given IV
Arm group label:
Treatment (Enfortumab vedotin)
Other name:
AGS 22ME
Other name:
AGS-22M6E
Other name:
Anti-Nectin 4 ADC ASG-22CE
Other name:
Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E
Other name:
ASG-22CE
Other name:
Enfortumab Vedotin-ejfv
Other name:
Padcev
Summary:
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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:
- 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
OR
- Any T, any N, M1
- 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:
- Unable to receive neoadjuvant (paclitaxel + ifosfamide + cisplatin) TIP because
of comorbidities or refused TIP; AND
- Unable to receive radiotherapy with curative intent, or refused radiotherapy
- 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:
- 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
- Failure to recover from any of the following therapies prior to registration:
- Major surgery
- Radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor
treatment with immunotherapy
- Immunocompromised patients and patients known to be human immunodeficiency virus
(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 (New York Heart
Association [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] 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Mayo Clinic Hospital in Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Cassandra N. Moore, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Winston W. Tan, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Lance C. Pagliaro, M.D.
Email:
Principal Investigator
Start date:
December 21, 2023
Completion date:
November 1, 2026
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06104618
https://www.mayo.edu/research/clinical-trials
