Evaluation of Lymphadenectomy and Chemotherapy TIP on Inguinal Lymph Nodes in Squamous Cell Carcinoma of the Penis

NCT02817958 | Active Not Recruiting Phase 2

• 3 other identifiers: UC-0160/1406AFU-GETUG 252014-004678-41
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 17

Brief Summary

Squamous cell carcinoma of the penis is a rare tumor in Europe, whose prognosis and survival are influenced by metastatic lymph node involvement. Its frequency in France is estimated at less than 1% of human cancers. This spread follows a sequential process via the superficial and deep inguinal lymph nodes and then to the pelvic lymph nodes before metastatic dissemination. The management of inguinal areas is the cornerstone of penile cancer. It is curative in about 80% of patients with 1 or 2 inguinal metastases. 5-years overall survival was on average 85% for pN0 patients and 40% for pN+ patients. For pN+ patients, 5-year overall survival was 70 to 80% for pN1 (only 1 lymph node invasion), 30 to 40% for pN2, and 0 to 10% for pN3. The risk of local recurrence is 5-10% for pN0 and 20-30% for pN+ after local treatment by lymphadenectomy alone without chemotherapy. The average time to recurrence was 10 months. Disease-free survival at 5 years is 75-85% for pN0 and 30-45% for pN+. Its indication depends on clinical examination (presence or absence of lymph nodes palpated) and the risk of nodal disease (≥pT1bG2). Currently, a fine needle biopsy is the best clinical diagnosis method because it is a simple, low risk, and possible in consultation. When the result is positive, it allows an early dissection. Single or double fine needle biopsy will be used in cN+ patients. For patients at risk of lymp nodes involvement (cN0 and ≥pT1B or G2), the sentinel node diagnosis may be followed by modified or bilateral lymphadenectomy. Although lymphadenectomy alone has a curator action, it sometimes remains insufficient in patients with metastatic lymph node involvement. Therefore it seems important to develop a multimodal approach in the management of these patients in order to increase the response rate to treatment and survival. From a Phase II trial conducted on 30 patients, the combination TIP (paclitaxel, ifosfamide, and cisplatin) appears to have an efficacy / toxicity acceptable. The TIP protocol has therefore been chosen for this trial as adjuvant or neo-adjuvant treatment in patients with high risk of lymph nodes involvement (cN0 and ≥pT1B or G2), and with inguinal mobile palpated lymph nodes (cN+) respectively, after lymph nodes involvement proven (pN+).

Conditions

Penile Cancer; Squamous Carcinoma

Keywords

inguinal lymph nodes; penile cancer; squamous; TIP chemotherapy

Outcome Measures

Primary Outcomes (1)

• survival without locoregional lymph node recurrence

  checked by inguinal ultrasound

  24 months

Secondary Outcomes (7)

• Complete response rate for patients in neoadjuvant chemotherapy

  6 months

• Survival without locoregional lymph node recurrence

  3 years

• Survival without metastasis

  3 years

• Specific survival

  3 years

• Overall survival

  3 years

Study Arms (2)

A-Adjuvant Chemotherapy TIP

EXPERIMENTAL

Lymphadenectomy (+/- sentinel node) + adjuvant chemotherapy TIP modified bilateral lymphadenectomy 4 cycles every 21 days

Drug: Chemotherapy TIP

B-Neoadjuvant Chemotherapy TIP

EXPERIMENTAL

fine needle biopsy or sentinel node + neoadjuvant chemotherapy TIP followed by a lymphadenectomy modified bilateral lymphadenectomy 4 cycles every 21 days

Drug: Chemotherapy TIP

Interventions

Chemotherapy TIP DRUG

Paclitaxel, ifosfamide, and cisplatin

Also known as: Chemotherapy TIP (paclitaxel, ifosfamide et cisplatine)

A-Adjuvant Chemotherapy TIP; B-Neoadjuvant Chemotherapy TIP

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• penile tumor histologically proven whatever the initial treatment of penile tumor: amputation or conservative surgery or brachytherapy,
• Mobile palpated lymph nodes (stage cN1 and cN2) whatever the T stage, Or If no palpated lymph nodes (cN0), patients with nodes involvement risk ≥pT1b and / or Grade 2,
• Metastatic lymph node involvement,
• Patients M0 or Mx,
• Age ≥18 ans,
• Eastern Cooperative Oncology Group (ECOG) 0-1,
• Leucocytes ≥1.5 g/L,
• Hemoglobin ≥9 g/dL,
• Platelets ≥100 000/mm³,
• Normal calcemia and kaliemia,
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 upper limit of normal (ULN) ; total bilirubin ≤1.5 ULN (3 ULN in case of Gilbert disease); alkaline phosphatase (ALP) \<2 ULN,
• Creatinine clearance ≥60 mL/min (MDRD method),
• Left ventricular ejection fraction (LVEF) \>50%,
• Patients having received, read the information note and signed consent,
• Reproductive age patients agreeing to use two methods of birth control (one for the patient and one for the partner) for the duration of the study and for 6 months after the last dose of treatment,

You may not qualify if:

• Fixed inguinal lymph nodes (cN3),
• Iliac lymph nodes (cN3),
• Patients pN3,
• prior chemotherapy for squamous cell carcinoma of the penis,
• Against-indication for chemotherapy or known hypersensitivity to cisplatin, ifosfamide or paclitaxel,
• Patients treated with phenytoin,
• Patients with hearing loss \>Grade 1 (CTCAE V4.03),
• Patients with cardiopulmonary disease-indicating against overhydration,
• Patients deprived of their liberty or under court protection including guardianship,
• Severe systemic disease or uncontrolled or any other chronic or acute illness that is incompatible with the patient's participation in the trial according to investigator,
• immunocompromised patients including with known seropositivity (HIV),

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator

Study Sites (17)

ICO-Paul Papin

Angers, 49055, France

Location

Chr Besancon

Besançon, 25000, France

Location

Hôpital SAINT ANDRE

Bordeaux, 33075, France

Location

Centre FRANCOIS BACLESSE

Caen, 14076, France

Location

Chru Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Ch de Limoges

Limoges, 87042, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Chu Lyon Sud

Lyon, 69310, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Institut de Cancerologie de Lorraine

Nancy, 54519, France

Location

Clinique Urologique- Chu Hotel Dieu

Nantes, 44093, France

Location

Institut de Cancerologie Du Gard - Centre Oncogard

Nîmes, 300029, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Chu de Rouen

Rouen, 76031, France

Location

ICO-René Gauducheau

Saint-Herblain, 44805, France

Location

Hopitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Penile Neoplasms; Carcinoma, Squamous Cell

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jérôme Rigaud, Professor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: June 29, 2016
• Study Start: October 17, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (17)