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

November 9, 2023 updated by: UNICANCER

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

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+).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Angers, France, 49055
        • Terminated
        • ICO-Paul Papin
      • Besançon, France, 25000
        • Recruiting
        • Chr Besancon
        • Contact:
      • Bordeaux, France, 33075
      • Caen, France, 14076
      • Clermont Ferrand, France, 63000
        • Recruiting
        • Chru Gabriel Montpied
        • Contact:
      • Limoges, France, 87042
      • Lyon, France, 69008
      • Lyon, France, 69310
      • Marseille, France, 13273
        • Recruiting
        • Institut Paoli-Calmettes
        • Contact:
      • Nancy, France, 54519
        • Recruiting
        • Institut de Cancérologie de Lorraine
        • Contact:
      • Nantes, France, 44093
        • Recruiting
        • Clinique Urologique- Chu Hotel Dieu
        • Contact:
      • Nîmes, France, 300029
        • Recruiting
        • Institut de Cancerologie Du Gard - Centre Oncogard
        • Contact:
      • Paris, France, 75010
        • Recruiting
        • Hôpital Saint Louis
        • Contact:
      • Rouen, France, 76031
      • Strasbourg, France, 67091
      • Toulouse, France, 31059
        • Terminated
        • Institut Claudius Regaud
      • saint Herblain, France, 44805

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
Other Names:
  • Chemotherapy TIP (paclitaxel, ifosfamide et cisplatine)
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
Other Names:
  • Chemotherapy TIP (paclitaxel, ifosfamide et cisplatine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
survival without locoregional lymph node recurrence
Time Frame: 24 months
checked by inguinal ultrasound
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate for patients in neoadjuvant chemotherapy
Time Frame: 6 months
lack of residual tumor post surgical histopathology
6 months
Survival without locoregional lymph node recurrence
Time Frame: 3 years
time between inclusion and locoregional recurrence or last evaluation
3 years
Survival without metastasis
Time Frame: 3 years
time between inclusion and the date of occurrence of metastases
3 years
Specific survival
Time Frame: 3 years
time between inclusion and date of death from penile cancer or treatment-related complication
3 years
Overall survival
Time Frame: 3 years
time between inclusion and the death regardless of cause
3 years
Acute and late toxicity during the study
Time Frame: Throughout study completion, up to 3 years

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v4.03) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3

= "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
Throughout study completion, up to 3 years
Quality of life questionnaire - Core 30 (QLQ-C30)
Time Frame: baseline, during treatment (C3J42), 6 month, 1 year
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
baseline, during treatment (C3J42), 6 month, 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Collaborators

National Cancer Institute, France

Investigators

  • Principal Investigator: Jérôme Rigaud, Professor, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2016

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

May 24, 2016

First Submitted That Met QC Criteria

June 24, 2016

First Posted (Estimated)

June 29, 2016

Study Record Updates

Last Update Posted (Actual)

November 13, 2023

Last Update Submitted That Met QC Criteria

November 9, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-0160/1406
  • AFU-GETUG 25 (Other Identifier: Unicancer)
  • 2014-004678-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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