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

Inclusion Criteria: 1. Age 18-75 2. Written informed consent 3. ECOG (Eastern Cooperative Oncology Group) performance status 0-1 4. Cytologically or histologically proven diagnosis of PSCC. 5. Histologically (Tru-cut biopsy) proven diagnosis of loco-regional nodal disease will be required in all cases except for those with clinical contraindications. 6. Uni- or bidimensionally measurable disease as defined by RECIST v1.1 criteria. 7. Clinical stage N2-3 and/or M1 (TNM 2002). 8. Locoregional relapse after prior major surgery/ies (either single or multiple). 9. 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. 10. Adequate organ and marrow function . 11. 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: 1. 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. 2. 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. 3. History of HIV infection or active chronic hepatitis B or C. 4. Active clinically serious infections (\> grade 2 NCI-CTC version 5.0). 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). 6. Patients undergoing renal dialysis 7. 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. 8. 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. 9. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 10. 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. 11. History of allogenic organ solid transplantation. 12. Fertile males not willing to use a highly effective method of contraception or whose female partner is not using a highly effective contraception protection. 13. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. 14. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study. 15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug. 16. 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. 17. Patients unable to swallow oral medications. 18. Concomitant anticoagulation with oral anticoagulants or platelet inhibitors. 19. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.