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

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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

Condition: Penile Cancer, Squamous Carcinoma

Intervention:

  • Drug: Chemotherapy TIP

Purpose: 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 +).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02817958

Sponsor: UNICANCER

Primary Outcome Measures:

  • Measure: survival without locoregional lymph node recurrence
  • Time Frame: 24 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Complete response rate for patients in neoadjuvant chemotherapy
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Survival without locoregional lymph node recurrence
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Survival without metastasis
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Specific survival
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Toxicity
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Quality of life
  • Time Frame: 1 year
  • Safety Issue:

Estimated Enrollment: 37

Study Start Date: April 2016

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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. 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 (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.

Contact:

  • Sandra PELISSIER
  • +33(0)144235568

Locations:

  • ICO-Paul Papin
  • Angers 49055 France
  • Chr Besancon
  • Besançon 25000 France
  • Hôpital SAINT ANDRE
  • Bordeaux 33075 France
  • Centre FRANCOIS BACLESSE
  • Caen 14076 France
  • Chru Gabriel Montpied
  • Clermont Ferrand 63000 France
  • Ch de Limoges
  • Limoges 87042 France
  • Centre Leon Berard
  • Lyon 69008 France
  • Chu Lyon Sud
  • Lyon 69310 France
  • Institut Paoli-Calmettes
  • Marseille 13273 France
  • Institut de Cancerologie de Lorraine
  • Nancy 54519 France
  • Clinique Urologique- Chu Hotel Dieu
  • Nantes 44093 France
  • Institut de Cancerologie Du Gard – Centre Oncogard
  • Nîmes 300029 France
  • Hopital Saint Louis
  • Paris 75010 France
  • Chu de Rouen
  • Rouen 76031 France
  • ICO-René Gauducheau
  • saint Herblain 44805 France
  • Hopitaux Universitaires de Strasbourg
  • Strasbourg 67091 France
  • Institut Claudius Regaud
  • Toulouse 31059 France

View trial on ClinicalTrials.gov

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