Patients with advanced penile squamous cell carcinoma (PSCC) MedDRA version: 21.1 Level: LLT Classification code 10049570 Term: Penile neoplasm NOS System Organ Class: 100000004864
Conditions
Sponsors
FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Age 18-75 2) Written informed consent 3) ECOG 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 chemotherapy (Vinblastine, Bleomycin, Methotrexate) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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 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 among those listed in the full protocol. 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. Note: Local surgery of isolated lesions for palliative intent is acceptable. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before inclusion. 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) P
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study will be to investigate the activity of daily oral doses of cabozantinib monotherapy until surgical removal of nodal disease (locally-advanced setting) or until disease progression or onset of unacceptable toxicity (metastatic setting).;Secondary Objective: To evaluate the safety and tolerability of cabozantinib monotherapy in a population of advanced patients with PSCC.;Primary end point(s): Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR, locally assessed by the investigator;Timepoint(s) of evaluation of this end point: Duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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.; Pathologic complete response (pCR) rate as assessed in locally advanced patients undergoing surgery; Progression-free survival (PFS).; Overall Survival (OS).; Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language.; Analysis of circulating biomarkers; Correlative endpoints;Timepoint(s) of evaluation of this end point: Duration of the study; Duration of the study; Duration of the study; Duration of the study.; Duration of the study.; Duration of the study; duration of the study | — |
Countries
Italy
Contacts
Public ContactClinical Trial Center
Fondazione IRCCS Istituto Nazionale dei Tumori
Outcome results
None listed