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

NCT ID: NCT02817958

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-17
• Study Completion Date: 2028-09-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

B-Neoadjuvant Chemotherapy TIP

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

Group Type: EXPERIMENTAL

Chemotherapy TIP

Intervention Type: DRUG

Paclitaxel, ifosfamide, and cisplatin

A-Adjuvant Chemotherapy TIP

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

Group Type: EXPERIMENTAL

Chemotherapy TIP

Intervention Type: DRUG

Paclitaxel, ifosfamide, and cisplatin

Interventions

Chemotherapy TIP

Paclitaxel, ifosfamide, and cisplatin

Intervention Type: DRUG

Other Intervention Names

Chemotherapy TIP (paclitaxel, ifosfamide et cisplatine)

Eligibility Criteria

Inclusion Criteria

1. penile tumor histologically proven whatever the initial treatment of penile tumor: amputation or conservative surgery or brachytherapy,

2. 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,

3. Metastatic lymph node involvement,

4. Patients M0 or Mx,

5. Age ≥18 ans,

6. Eastern Cooperative Oncology Group (ECOG) 0-1,

7. Leucocytes ≥1.5 g/L,

8. Hemoglobin ≥9 g/dL,

9. Platelets ≥100 000/mm³,

10. Normal calcemia and kaliemia,

11. 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,

12. Creatinine clearance ≥60 mL/min (MDRD method),

13. Left ventricular ejection fraction (LVEF) >50%,

14. Patients having received, read the information note and signed consent,

15. 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,

16. Patients able to comply with the protocol requirements (scheduled visits, treatment plan, clinical, paraclinical, biological and other procedures of the Protocol),

17. Patients undergoing a social security scheme.

Exclusion Criteria

1. Fixed inguinal lymph nodes (cN3),

2. Iliac lymph nodes (cN3),

3. Patients pN3,

4. prior chemotherapy for squamous cell carcinoma of the penis,

5. Against-indication for chemotherapy or known hypersensitivity to cisplatin, ifosfamide or paclitaxel,

6. Patients treated with phenytoin,

7. Patients with hearing loss >Grade 1 (CTCAE V4.03),

8. Patients with cardiopulmonary disease-indicating against overhydration,

9. History of cancer within 5 years prior to inclusion in the trial other than cutaneous basal cell,

10. Patient received a live attenuated vaccine within 30 days prior to inclusion,

11. Patients already included in another clinical trial or receiving an experimental treatment within 30 days prior to inclusion in the trial,

12. Patients deprived of their liberty or under court protection including guardianship,

13. 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,

14. immunocompromised patients including with known seropositivity (HIV),

15. Patients with mental impairment which prevents the understanding of the protocol or having a psychological state, family, sociological or geographical conditions that would not allow compliance with the protocol and the planned follow-up or any condition which, according to the investigator, would prevent participation patient tested. These conditions should be assessed before inclusion of patients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jérôme Rigaud, Professor

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

ICO-Paul Papin

Angers, , France

Chr Besancon

Besançon, , France

Hôpital SAINT ANDRE

Bordeaux, , France

Centre FRANCOIS BACLESSE

Caen, , France

Chru Gabriel Montpied

Clermont-Ferrand, , France

Ch de Limoges

Limoges, , France

Centre Leon Berard

Lyon, , France

Chu Lyon Sud

Lyon, , France

Institut Paoli-Calmettes

Marseille, , France

Institut de Cancerologie de Lorraine

Nancy, , France

Clinique Urologique- Chu Hotel Dieu

Nantes, , France

Institut de Cancerologie Du Gard - Centre Oncogard

Nîmes, , France

Hopital Saint Louis

Paris, , France

Chu de Rouen

Rouen, , France

ICO-René Gauducheau

Saint-Herblain, , France

Hopitaux Universitaires de Strasbourg

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Countries

France

Other Identifiers

UC-0160/1406

Identifier Type: -

Identifier Source: org_study_id

AFU-GETUG 25

Identifier Type: OTHER

Identifier Source: secondary_id

2014-004678-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id