Cabozantinib in Patients With Advanced Penile Squamous Cell Carcinoma (PSCC) (CaboPen)

Study Overview
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Brief Summary
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Cabozantinib in patients with advanced penile squamous cell carcinoma (PSCC): an open-label, single-center, phase 2, single-arm trial (CaboPen)

Detailed Description
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an open-label, single-center, phase 2, single-arm trial

Official Title
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Cabozantinib in Patients With Advanced Penile Squamous Cell Carcinoma (PSCC): an Open-label, Single-center, Phase 2, Single-arm Trial (CaboPen)

Conditions
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Penile Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cabozantinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 Written informed consent ECOG (Eastern Cooperative Oncology Group) performance status 0-1 Cytologically or histologically proven diagnosis of PSCC. Histologically (Tru-cut biopsy) proven diagnosis of loco-regional nodal disease will be required in all cases except for those with clinical contraindications. Uni- or bidimensionally measurable disease as defined by RECIST v1.1 criteria. Clinical stage N2-3 and/or M1 (TNM 2002). Locoregional relapse after prior major surgery/ies (either single or multiple). No prior systemic therapy except for the administration of VBM (Vinblastine, Bleomycin, Methotrexate) chemotherapy for superficial disease if administered at least 6 months prior to study enrolment. Adequate organ and marrow function . Patients must be accessible for treatment and follow up as well as they must be willing and capable to comply with the requirements of the study. Patients registered on this trial must be treated and followed at the study sponsor site. Exclusion Criteria: History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting. Myocardial infarction. Unstable angina. Coronary artery by-pass graft surgery. Symptomatic peripheral vascular disease. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted during the study but should be used with caution - please refer to the study drug IB). Screening ECG with a QTc>450 msec, congenital long QT syndrome, history of sustained ventricular tachycardia, history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate < 50 bpm (patients with a pacemaker and heart rate > 50 bpm are eligible). Uncontrolled hypertension. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months ior to first dose of study drug. History of HIV infection or active chronic hepatitis B or C. Active clinically serious infections (> grade 2 NCI-CTC version 5.0). Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). Patients undergoing renal dialysis Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT treated basal cell carcinoma or any cancer curatively treated > 5 years prior to study entry. History of clinically-significant gastrointestinal bleeding, inflammatory bowel disease, and other GI disorders associated with high risk of perforation or fistula formation or any other condition. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Major surgery within 12 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment. Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. History of allogenic organ solid transplantation. Fertile males not willing to use a highly effective method of contraception or whose female partner is not using a highly effective contraception protection. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug. Hemoptysis >=2.5 ml red blood within 3 months before treatment, signs indicative of pulmonary hemorrhage, cavitating pulmonary lesion, tumor invading major blood vessels and/or GI tract, endotracheal or endobronchial tumors History of clinically-significant gastrointestinal bleeding, inflammatory bowel disease, or any other condition among those listed in the full protocol. Patients unable to swallow oral medications. Concomitant anticoagulation with oral anticoagulants or platelet inhibitors. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib<br>Cabozantinib will be administered orally at a dose of 60 mg/day continuously until 28 days prior to planned surgery or at time of the evidence of disease progression or onset of unacceptable toxicity. | Drug: Cabozantinib<br>* Cabozantinib 60 mg/day orally<br>* Other names: CABOMETYX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response -rate by RECIST v1.1 criteria | Assessment of response-rate by RECIST v1.1. Complete response + partial response | 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-Emergent Adverse Event(safety and tolerability) | Assessment of the safety and tolerability: incidence, nature and severity of treatment-related adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | 40 months | 
| Pathologic complete response (pCR) | Histological report of radical surgery | 40 months | 
| Progression-free survival (PFS). | Recist 1.1 criteria | 40 months | 
| Overall Survival (OS). | time will be calculated as the interval from treatment start date to the date of death for any cause, with censoring at the date of last contact for patients alive. | 40 months | 
| Variations of the Quality of Life | Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language. In this quality of life there are specify 9 main symptons: the score range is from 0 to 10 for each one. For each symptom the 0 score corrisponds to no symptom present (better outcome) and the 10 score corrisponds to maximum symptom assessable (worse outcome). The listed symptoms are: 1) Pain 2) Fatigue 3) Nausea 4) Depression 5) Anxiety 6) Somnolence 7) Loss of appetite 8) General Malaise 9) Dispnea. The total score is ranging from 0 to 90 | 40 months | 
| FDG-PET/CT response rate according to EORTC criteria | to determine the rate of concordance with CT scan RECIST 1.1 response criteria and PET/CT EORTC Criteria Complete response: complete disappearance of all target lesions with the exception of nodal disease (RECIST 1.1) and Complete resolution of FDG uptake in all lesions (EORTC) Partial response (PR): greater than or equal to 30% decrease under baseline of the sum of target lesions (RECIST 1.1) and ≥ 25% reduction in the sum of SUVmax Stable disease (SD): Not qualify for CR, PR or PD Objective Progression (PD): 20% increase in the sum of diameters of target lesions or appearance of new unequivocal malignant lesions (RECIST 1.1) and ≥ 25% Increase in the sum of SUVmax or appearance of new lesions. To evaluate the relationship existing between tumor response measured by FDG-PET/CT EORTC Criteria (mainly early PET response as evaluated at first restaging) and pCR-rate (pT0 after surgery) and progression-free survival (months). | 40 months |