VinCaP is a multicentre single-arm phase II trial. 22 patients will receive Vinflunine chemotherapy (Vinflunine 320mg/m2 given intravenously on day 1 of each cycle of 21 days, four cycles to be given prior to formal re-staging).

Inclusion Criteria:

1. Male, ≥18 years.

2. Measurable disease as determined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria (version 1.1).

3. Patients who present with purely cutaneous measurable disease should fulfill RECIST Criteria (see Appendix 1). Lesions should be a minimum size of 10 mm and measured using calipers by clinical examination.

4. Histologically-proven squamous cell carcinoma of the penis.

5. Stage: M1, or; M0, any T, N3 (i.e. involvement of deep inguinal or pelvic lymph nodes) or; M0, any T, N2 (i.e. involvement of multiple or bilateral superficial lymph nodes) or; M0, T4 (tumour invades other adjacent structures) any N.

   Notes:

   1. Patients with M0 disease may be considered if, in the opinion of the specialist Multi Disciplinary Team (MDT), they are deemed unlikely to benefit from surgery with curative intent and unlikely to tolerate combination chemotherapy due to comorbidities and/or disease burden.
   2. Patients who have received prior radiotherapy to non-target lesions may be included.

6. Pre-treatment blood counts, haematology and biochemistry values within the following acceptable limits: Absolute Neutrophil Count (ANC) ≥ 1,500/mm3, Platelets ≥100,000/mm3, glomerular filtration rate (GFR) ≥60ml/min. GFR to be assessed according to local practice (recommended technique of eGFR using the MDRD formula.

7. Liver function: Patients must have (with or without the presence of liver metastases):

   • A prothrombin time >70% normal value (NV) AND
   • Bilirubin <1.5xUpper Limit of Normal (ULN) AND
   • Transaminases <2.5xULN AND
   • GGT <5xULN

8. Performance Status Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2.

9. Written, informed consent.

Exclusion Criteria:

1. Pure verrucous carcinoma of the penis.

2. Squamous carcinoma of the urethra.

3. Patients who do not have measurable disease as determined by RECIST (version 1.1).

4. T1 N1 M0 disease.

5. T2 N1 M0 disease.

6. M0, T3, N1 (tumour invades urethra or prostate and single inguinal node involved).

7. Unfit for vinflunine chemotherapy (as assessed by the multidisciplinary team).

8. Previous chemotherapy or chemoradiotherapy.

9. Contraindication to chemotherapy.

10. Other malignancy (other than Squamous Cell Carcinoma or Basal Cell Carcinoma of non-penile skin) that has required surgical or non-surgical treatment in the last 5 years. All patients with a previous cancer diagnosis must be discussed the Chief Investigator prior to entry into the trial.

11. Patients who have received radiotherapy to target lesions and have no other lesions that can act as target lesions instead:

    e.g. Patients with recurrent pelvic lymph nodes that are deemed irresectable and who have had prior radiotherapy to those lymph nodes:

    i. are INELIGIBLE if the involved lymph nodes are the only site of disease.

    ii. are ELIGIBLE if they have other measurable sites of disease e.g. pulmonary metastases.

    If uncertain, please discuss with the Chief Investigator.