This trial is active, not recruiting.

Conditions penile cancer, squamous carcinoma
Treatment chemotherapie tip
Phase phase 2
Collaborator National Cancer Institute, France
Start date April 2016
End date September 2021
Trial size 37 participants
Trial identifier NCT02817958, AFU-GETUG 25, UC-0160/1406


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-years overall survival was 70 to 80% for pN1 (only 1 lymph node invasion), and 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 +).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Lymphadenectomy (+/- sentinel node) + adjuvant chemotherapie TIP modified bilateral lymphadenectomy 4 cycles every 21 days
chemotherapie tip
Paclitaxel, ifosfamide and cisplatine
fine needle biopsy or sentinel node + neoadjuvant chemotherapie TIP followed by a lymphadenectomy modified bilateral lymphadenectomy 4 cycles every 21 days
chemotherapie tip
Paclitaxel, ifosfamide and cisplatine

Primary Outcomes

survival without locoregional lymph node recurrence
time frame: 24 months

Secondary Outcomes

Complete response rate for patients in neoadjuvant chemotherapy
time frame: 6 months
Survival without locoregional lymph node recurrence
time frame: 3 years
Survival without metastasis
time frame: 3 years
Specific survival
time frame: 3 years
Overall survival
time frame: 3 years
time frame: 3 years
Quality of life
time frame: 1 year

Eligibility Criteria

Male participants at least 18 years old.

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. 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. AST and ALT ≤ 1.5 LNS ; total bilirubin ≤ 1.5 LNS (3 LNS in case of Gilbert disease); PAL < 2 LNS, 12. Creatinine clearance ≥ 60 mL/mn (MDRD method), 13. FEVG > 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 (CTC-AE 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 lyberty 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.

Additional Information

Official title Prospective Phase II Study Evaluating a Multimodal Care of Inguinal Node Metastasis in Squamous Cell Carcinoma of the Penis by Bilateral Lymphadenectomy and Chemotherapy TIP
Principal investigator Jérôme Rigaud, Professor
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by UNICANCER.