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

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ClinicalTrials.gov Identifier: NCT02817958
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : September 28, 2021
National Cancer Institute, France
Information provided by (Responsible Party):

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+).

Condition or disease Intervention/treatment Phase
Penile Cancer Squamous Carcinoma Drug: Chemotherapy TIP Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 17, 2016
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: A-Adjuvant Chemotherapy TIP
Lymphadenectomy (+/- sentinel node) + adjuvant chemotherapy TIP modified bilateral lymphadenectomy 4 cycles every 21 days
Drug: Chemotherapy TIP
Paclitaxel, ifosfamide, and cisplatin

Experimental: 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
Drug: Chemotherapy TIP
Paclitaxel, ifosfamide, and cisplatin

Primary Outcome Measures :
  1. survival without locoregional lymph node recurrence [ Time Frame: 24 months ]
    checked by inguinal ultrasound

Secondary Outcome Measures :
  1. Complete response rate for patients in neoadjuvant chemotherapy [ Time Frame: 6 months ]
    lack of residual tumor post surgical histopathology

  2. Survival without locoregional lymph node recurrence [ Time Frame: 3 years ]
    time between inclusion and locoregional recurrence or last evaluation

  3. Survival without metastasis [ Time Frame: 3 years ]
    time between inclusion and the date of occurrence of metastases

  4. Specific survival [ Time Frame: 3 years ]
    time between inclusion and date of death from penile cancer or treatment-related complication

  5. Overall survival [ Time Frame: 3 years ]
    time between inclusion and the death regardless of cause

  6. Toxicity [ Time Frame: 3 years ]
    Common Terminology Criteria for Adverse Events (CTCAE ) v4.03

  7. Quality of life [ Time Frame: 1 year ]
    questionnaire EORTC QLQ-C30 v3

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02817958

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Contact: Sandra PELISSIER +33(0)144235568 s-pelissier@unicancer.fr

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Sponsors and Collaborators
National Cancer Institute, France
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Principal Investigator: Jérôme Rigaud, Professor CHU de Nantes
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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT02817958    
Other Study ID Numbers: UC-0160/1406
AFU-GETUG 25 ( Other Identifier: Unicancer )
2014-004678-41 ( EudraCT Number )
First Posted: June 29, 2016    Key Record Dates
Last Update Posted: September 28, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
inguinal lymph nodes
penile cancer
TIP chemotherapy
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Penile Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Penile Diseases