A Phase II Trial of Vinflunine Chemotherapy in Locally-advanced and Metastatic Carcinoma of the Penis (VinCaP) (VinCaP)

A Phase II Trial of Vinflunine Chemotherapy in Locally-advanced and Metastatic Carcinoma of the Penis

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).

Study Overview

• Status: Completed
• Conditions: Locally-advanced or Metastatic Penile Neoplasms
• Intervention / Treatment: Drug: Vinflunine

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom, LS79 7TF
    • St James's University Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Cardiff
    • Whitchurch, Cardiff, United Kingdom, CF14 2TL
      • Velindre NHS Trust
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospitals NHS Trust
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • University College London Hospitals Nhs Foundation Trust
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie Nhs Foundation Trust
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • St George's Healthcare NHS Trust
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vinflunine; All patients will receive on Day 1 of a 21 day cycle, vinflunine 320mg/m2 via intravenous infusion in either 100ml sodium chloride 0.9% or glucose 5% over 20 minutes; four cycles to be given in total prior to formal re-staging.	Drug: Vinflunine; All patients will receive on Day 1 of a 21 day cycle, vinflunine 320mg/m2 via intravenous infusion in either 100ml sodium chloride 0.9% or glucose 5% over 20 minutes; four cycles to be given in total prior to formal re-staging.; Other Names: Javlor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit	To determine the clinical benefit (objective response & stable disease rate) and toxicity of vinflunine in patients with inoperable (locally advanced or metastatic) cancer of the penis and thus determine whether this drug warrants further research in this indication.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Proportion of patients having achieved partial or complete remission. The proportion of patients with objective response will be calculated and presented along its 95% confidence interval.	12 weeks
Toxicity	Toxicity will be evaluated, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4 scoring, after each cycle, at the end of treatment and at follow up visits. The proportion of patients experiencing grade 3 or 4 toxicities at these time points and until progression will be reported as well as the Serious Adverse Events (SAEs).	Baseline, 3, 6, 9, 12 weeks on treatment, and at follow-up, 3, 6, 9, 12, 18, 24 months (timed from end of last cycle of chemotherapy)
Progression-free survival	Progression-free survival will be defined as time from registration until the first of clinically or radiologically documented disease progression, or death from any cause death. Patients alive and progression-free at time of analysis will be censored at date last seen.	From registration to first documented disease progression or death from any cause, up to 24 months
Overall Survival	Patients alive at time of analysis will be censored at date last seen. Patients lost to follow-up will be censored at date last seen.	Time from registration until death from any cause, up to 24 months
Treatment Compliance	Treatment Compliance will be defined as proportion of planned doses delivered. Reasons for non-delivery of planned doses (patient or clinician preference, toxicity and tolerability) will be collected.	12 weeks

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: St George's Healthcare NHS Trust
• Investigators: Principal Investigator: Lisa Pickering, MBBS, MRCP, St George's Healthcare NHS Trust

Publications and helpful links

General Publications

• Nicholson S, Tovey H, Elliott T, Burnett SM, Cruickshank C, Bahl A, Kirkbride P, Mitra AV, Thomson AH, Vasudev N, Venugopal B, Slade R, Tregellas L, Morgan B, Hassall A, Hall E, Pickering LM. VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis. Br J Cancer. 2022 Jan;126(1):34-41. doi: 10.1038/s41416-021-01574-9. Epub 2021 Oct 20.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2014
• Primary Completion (Actual): November 6, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Chemotherapy; Phase II; Vinflunine; Penile neoplasms
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Penile Diseases; Penile Neoplasms
• Other Study ID Numbers: ICR-CTSU/2012/10036; CRUK/12/021 (Other Grant/Funding Number: Cancer Research UK); 2012-002592-34 (EudraCT Number); 13/LO/0822 (Other Identifier: Main REC number); CCR3858 (Other Identifier: Sponsor Number)