Evaluation of Lymphadenectomy and Chemotherapy TIP on Inguinal Lymph Nodes in Squamous Cell Carcinoma of the Penis (MEGACEP)
Primary Purpose
Penile Cancer, Squamous Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Chemotherapy TIP
Sponsored by
About this trial
This is an interventional treatment trial for Penile Cancer focused on measuring inguinal lymph nodes, penile cancer, squamous, TIP chemotherapy
Eligibility Criteria
Inclusion Criteria:
- penile tumor histologically proven whatever the initial treatment of penile tumor: amputation or conservative surgery or brachytherapy,
- 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,
- Metastatic lymph node involvement,
- Patients M0 or Mx,
- Age ≥18 ans,
- Eastern Cooperative Oncology Group (ECOG) 0-1,
- Leucocytes ≥1.5 g/L,
- Hemoglobin ≥9 g/dL,
- Platelets ≥100 000/mm³,
- Normal calcemia and kaliemia,
- 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,
- Creatinine clearance ≥60 mL/min (MDRD method),
- Left ventricular ejection fraction (LVEF) >50%,
- Patients having received, read the information note and signed consent,
- 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,
- Patients able to comply with the protocol requirements (scheduled visits, treatment plan, clinical, paraclinical, biological and other procedures of the Protocol),
- Patients undergoing a social security scheme.
Exclusion Criteria:
- Fixed inguinal lymph nodes (cN3),
- Iliac lymph nodes (cN3),
- Patients pN3,
- prior chemotherapy for squamous cell carcinoma of the penis,
- Against-indication for chemotherapy or known hypersensitivity to cisplatin, ifosfamide or paclitaxel,
- Patients treated with phenytoin,
- Patients with hearing loss >Grade 1 (CTCAE V4.03),
- Patients with cardiopulmonary disease-indicating against overhydration,
- History of cancer within 5 years prior to inclusion in the trial other than cutaneous basal cell,
- Patient received a live attenuated vaccine within 30 days prior to inclusion,
- Patients already included in another clinical trial or receiving an experimental treatment within 30 days prior to inclusion in the trial,
- Patients deprived of their liberty or under court protection including guardianship,
- 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,
- immunocompromised patients including with known seropositivity (HIV),
- 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.
Sites / Locations
- ICO-Paul Papin
- Chr BesanconRecruiting
- Hôpital SAINT ANDRERecruiting
- Centre FRANCOIS BACLESSERecruiting
- Chru Gabriel MontpiedRecruiting
- Ch de LimogesRecruiting
- Centre Leon BerardRecruiting
- Chu Lyon SudRecruiting
- Institut Paoli-CalmettesRecruiting
- Institut de Cancerologie de LorraineRecruiting
- Clinique Urologique- Chu Hotel DieuRecruiting
- Institut de Cancerologie Du Gard - Centre OncogardRecruiting
- Hopital Saint LouisRecruiting
- Chu de RouenRecruiting
- ICO-René GauducheauRecruiting
- Hopitaux Universitaires de StrasbourgRecruiting
- Institut Claudius Regaud
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
A-Adjuvant Chemotherapy TIP
B-Neoadjuvant Chemotherapy TIP
Arm Description
Lymphadenectomy (+/- sentinel node) + adjuvant chemotherapy TIP modified bilateral lymphadenectomy 4 cycles every 21 days
fine needle biopsy or sentinel node + neoadjuvant chemotherapy TIP followed by a lymphadenectomy modified bilateral lymphadenectomy 4 cycles every 21 days
Outcomes
Primary Outcome Measures
survival without locoregional lymph node recurrence
checked by inguinal ultrasound
Secondary Outcome Measures
Complete response rate for patients in neoadjuvant chemotherapy
lack of residual tumor post surgical histopathology
Survival without locoregional lymph node recurrence
time between inclusion and locoregional recurrence or last evaluation
Survival without metastasis
time between inclusion and the date of occurrence of metastases
Specific survival
time between inclusion and date of death from penile cancer or treatment-related complication
Overall survival
time between inclusion and the death regardless of cause
Toxicity
Common Terminology Criteria for Adverse Events (CTCAE ) v4.03
Quality of life
questionnaire EORTC QLQ-C30 v3
Full Information
NCT ID
NCT02817958
First Posted
May 24, 2016
Last Updated
October 24, 2022
Sponsor
UNICANCER
Collaborators
National Cancer Institute, France
1. Study Identification
Unique Protocol Identification Number
NCT02817958
Brief Title
Evaluation of Lymphadenectomy and Chemotherapy TIP on Inguinal Lymph Nodes in Squamous Cell Carcinoma of the Penis
Acronym
MEGACEP
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 17, 2016 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
Collaborators
National Cancer Institute, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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+).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Penile Cancer, Squamous Carcinoma
Keywords
inguinal lymph nodes, penile cancer, squamous, TIP chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A-Adjuvant Chemotherapy TIP
Arm Type
Experimental
Arm Description
Lymphadenectomy (+/- sentinel node) + adjuvant chemotherapy TIP modified bilateral lymphadenectomy 4 cycles every 21 days
Arm Title
B-Neoadjuvant Chemotherapy TIP
Arm Type
Experimental
Arm Description
fine needle biopsy or sentinel node + neoadjuvant chemotherapy TIP followed by a lymphadenectomy modified bilateral lymphadenectomy 4 cycles every 21 days
Intervention Type
Drug
Intervention Name(s)
Chemotherapy TIP
Intervention Description
Paclitaxel, ifosfamide, and cisplatin
Primary Outcome Measure Information:
Title
survival without locoregional lymph node recurrence
Description
checked by inguinal ultrasound
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Complete response rate for patients in neoadjuvant chemotherapy
Description
lack of residual tumor post surgical histopathology
Time Frame
6 months
Title
Survival without locoregional lymph node recurrence
Description
time between inclusion and locoregional recurrence or last evaluation
Time Frame
3 years
Title
Survival without metastasis
Description
time between inclusion and the date of occurrence of metastases
Time Frame
3 years
Title
Specific survival
Description
time between inclusion and date of death from penile cancer or treatment-related complication
Time Frame
3 years
Title
Overall survival
Description
time between inclusion and the death regardless of cause
Time Frame
3 years
Title
Toxicity
Description
Common Terminology Criteria for Adverse Events (CTCAE ) v4.03
Time Frame
3 years
Title
Quality of life
Description
questionnaire EORTC QLQ-C30 v3
Time Frame
1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
penile tumor histologically proven whatever the initial treatment of penile tumor: amputation or conservative surgery or brachytherapy,
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,
Metastatic lymph node involvement,
Patients M0 or Mx,
Age ≥18 ans,
Eastern Cooperative Oncology Group (ECOG) 0-1,
Leucocytes ≥1.5 g/L,
Hemoglobin ≥9 g/dL,
Platelets ≥100 000/mm³,
Normal calcemia and kaliemia,
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,
Creatinine clearance ≥60 mL/min (MDRD method),
Left ventricular ejection fraction (LVEF) >50%,
Patients having received, read the information note and signed consent,
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,
Patients able to comply with the protocol requirements (scheduled visits, treatment plan, clinical, paraclinical, biological and other procedures of the Protocol),
Patients undergoing a social security scheme.
Exclusion Criteria:
Fixed inguinal lymph nodes (cN3),
Iliac lymph nodes (cN3),
Patients pN3,
prior chemotherapy for squamous cell carcinoma of the penis,
Against-indication for chemotherapy or known hypersensitivity to cisplatin, ifosfamide or paclitaxel,
Patients treated with phenytoin,
Patients with hearing loss >Grade 1 (CTCAE V4.03),
Patients with cardiopulmonary disease-indicating against overhydration,
History of cancer within 5 years prior to inclusion in the trial other than cutaneous basal cell,
Patient received a live attenuated vaccine within 30 days prior to inclusion,
Patients already included in another clinical trial or receiving an experimental treatment within 30 days prior to inclusion in the trial,
Patients deprived of their liberty or under court protection including guardianship,
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,
immunocompromised patients including with known seropositivity (HIV),
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra PELISSIER
Phone
+33(0)144235568
Email
s-pelissier@unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jérôme Rigaud, Professor
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICO-Paul Papin
City
Angers
ZIP/Postal Code
49055
Country
France
Individual Site Status
Terminated
Facility Name
Chr Besancon
City
Besançon
ZIP/Postal Code
25000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tristant MAURINA, Doctor
Phone
+33(0)3 81 66 93 67
Email
t1maurina@chu-besancon.fr
Facility Name
Hôpital SAINT ANDRE
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amaury DASTE, Doctor
Email
amaury.daste@chu-bordeaux.fr
Facility Name
Centre FRANCOIS BACLESSE
City
Caen
ZIP/Postal Code
14076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florence JOLY, Prof
Phone
+33 2 31 45 50 02
Email
f.joly@baclesse.unicancer.fr
Facility Name
Chru Gabriel Montpied
City
Clermont Ferrand
ZIP/Postal Code
63000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent GUY, Professor
Phone
+33(0)4 73 75 14 97
Email
lguy@chu-clermontferrand.fr
Facility Name
Ch de Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurélien DESCAZEAUD, Professor
Phone
+33(0)5 55 05 80 15
Email
aurelien.descazeaud@chu-limoges.fr
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aude FLECHON, Doctor
Phone
+33(0)4 78 78 26 43
Email
aude.flechon@lyon.unicancer.fr
Facility Name
Chu Lyon Sud
City
Lyon
ZIP/Postal Code
69310
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Etienne TERRIER, Dr
Phone
+33 4 72 67 88 01
Email
jean-etienne.terrier01@chu-lyon.fr
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gwenaelle GRAVIS, Doctor
Phone
+33(0)4 91 22 37 40
Email
gravisg@ipc.unicancer.fr
Facility Name
Institut de Cancerologie de Lorraine
City
Nancy
ZIP/Postal Code
54519
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent MASSARD, Dr
Phone
+33 3 23 59 84 61
Email
v.massard@nancy.unicancer.fr
Facility Name
Clinique Urologique- Chu Hotel Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jérôme RIGAUD, Professor
Phone
+33(0)2 40 08 39 10
Email
jrigaud@chu-nantes.fr
Facility Name
Institut de Cancerologie Du Gard - Centre Oncogard
City
Nîmes
ZIP/Postal Code
300029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angélique CHAPELLE, Doctor
Phone
+33(0)4 30 06 10 14
Email
a.chapelle@oncogard.com
Facility Name
Hopital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stéphane CULINE, Professor
Phone
+33(0)1 42 49 42 47
Email
stephane.culine@aphp.fr
Facility Name
Chu de Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian PFISTER, Professor
Phone
+33(0)2 32 88 81 63
Email
christian.pfister@chu-rouen.fr
Facility Name
ICO-René Gauducheau
City
saint Herblain
ZIP/Postal Code
44805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuelle BOMPAS, Doctor
Phone
+33(0)2 40 67 97 00
Email
emmanuelle.bompas@ico.unicancer.fr
Facility Name
Hopitaux Universitaires de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe BARTHELEMY, Doctor
Email
philippe.barthelemy@chru-strasbourg.fr
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Terminated
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Learn more about this trial
Evaluation of Lymphadenectomy and Chemotherapy TIP on Inguinal Lymph Nodes in Squamous Cell Carcinoma of the Penis
We'll reach out to this number within 24 hrs