Trial Title:
De-escalation Study for Stage IIa/IIb < 3 cm Seminoma
NCT ID:
NCT05529251
Condition:
Seminoma
Stage II
Conditions: Official terms:
Seminoma
Carboplatin
Conditions: Keywords:
De-escalation
Chemotherapy
Radiotherapy
Carboplatin
Etoposide
Cisplatine
Micro-RNA-M371
PET scan
Overall survival
Biomarker
Efficacy
Progression free rate
Safety
Quality of life
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
- In case of negative week-3 (after 1 EP cyle) PET-scan: Randomization according to 2
arms
1. Boost of radiotherapy 20 to 30 Gray (Gy) (ARM A)
2. Carboplatin AUC7 chemotherapy (ARM B)
- In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C)
Parallel observational cohort for patients scheduled to receive standard lumbo-aortic
radiotherapy after orchiectomy
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Radiotherapy boost
Description:
Radiotherapy boost 20 to 30 Gy, in daily 2 Gy fractions and 5 fractions per week :
- 20 Gy if no more disease is visible (node < 1 cm in large diameter)
- 24 Gy for nodes <= 2 cm
- 30 Gy for nodes > 2 cm
Arm group label:
ARM A
Intervention type:
Drug
Intervention name:
Carboplatin AUC7
Description:
Carboplatin at dose (mg) = AUC7 (mg/ml x min) x (DFG ml/min + 25)
Arm group label:
ARM B
Intervention type:
Drug
Intervention name:
3 cycles of EP
Description:
3 Cycles of EP chemotherapy, administred every 3 weeks following standard practice
Arm group label:
ARM C
Summary:
Phase II, multicenter, prospective, randomized, non-comparative, de-escalation study.
Patients with stage IIa/IIb < 3 cm seminoma histologically proved after orchiectomy will
be included in the study and will receive 1 cycle of Etoposide Cisplatine (EP)
chemotherapy.
Patients with negative week-3 PET-scan after the EP cycle, will be randomized (1:1 ratio,
stratification according to the disease stage (stage IIa versus IIb seminoma)) to receive
either radiotherapy (RT) boost on lymph nodes or 1 cycle of carboplatin AUC7
chemotherapy.
Patients with positive week-3 PET-scan will received 3 additional cycles of EP
chemotherapy.
In parallel, eligible patients scheduled to receive standard lombo-aortic RT will be
registered in an observational cohort.
Detailed description:
Stage II seminoma is defined by the presence of retroperitoneal lymph node metastases. It
concerns approximately 15% of patients with seminoma. The standard treatment for patients
with stage IIa/b seminoma, after orchiectomy, is extended lumbo-aortic/ipsilateral iliac
radiotherapy (RT). Performing chemotherapy (CT) with 3 courses of
Bleomycin-Etoposide-Cisplatin (BEP) or 4 courses of Etoposide-Cisplatin (EP) is an
alternative.
The optimal treatment choice remains controversial. Both treatment modalities are
associated with excellent efficacy but also acute and late toxicities. European Society
of Medical Oncology (ESMO) guidelines recommended in equal measure CT and RT for stage
IIa. A recent systematic review concluded that RT and cisplatin-based combination CT are
equally effective in clinical stage IIa/IIb seminoma, with a trend in favor of
chemotherapy in stage IIb because of lower relapse rate. However, due to the rarity of
stage II seminoma, a sufficiently powered randomized trial comparing radiotherapy with
chemotherapy is unlikely to be completed.
De-escalation strategies are required to minimize acute and long-term toxicities while
maintaining efficacy. De-escalated treatment for seminoma patients with stage IIb/IIC/III
and good prognosis according to International Germ Cell Cancer Collaborative Group
(IGCCCG), based on negative PET after 2 cycles of EP chemotherapy, is feasible and safe
according to SEMITEP results (cohort 2). In case of negative PET, 1 additional cycle of
CT with carboplatin AUC7 was administered.
Furthermore, serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly
associated with clinical stage, primary tumor size and response to treatment in
testicular germ cell tumors, with sensitivity and specificity higher than those of
classic markers (hCGt, LDH). However, further evaluations are needed before modifying
clinical practices.
We propose to conduct a multicenter, prospective, randomized, non-comparative,
de-escalation phase II study in patients with stage IIa/IIb seminoma < 3 cm, evaluating:
- a more de-escalated CT treatment: 1 cycle of EP followed, in case of negative PET,
by either a boost of RT on lymph node or 1 cycle of carboplatin AUC7
- the biomarker miRNA-M371 in therapeutic decision and correlation with PET.
In parallel, eligible patients scheduled to receive standard lombo-aortic RT will be
registered in an observational cohort.
Criteria for eligibility:
Criteria:
Inclusion criteria :
1. Age ≥ 18 years on the day of signing informed consent.
2. Primary testicular seminomatous germ cell tumor.
3. Stage IIa/IIb < 3 cm in largest diameter seminoma, histologically proved after
orchiectomy.
4. Confirmation of a progressive disease (positive PET scan or increase of lymph nodes
size by two successive CT scan).
5. Good prognosis according to IGCCCG and LDH < 2.5 x Upper Limit of Normal (ULN).
6. Normal alpha-fetoprotein (AFP) before and after orchiectomy.
7. No prior treatment with radiotherapy or chemotherapy.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
9. Adequate bone-marrow, hepatic, and renal functions with:
- Neutrophils ≥ 1.5 x Giga/l, platelets ≥ 100 x Giga/l,
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 1,5 x
ULN,
- Serum creatinine < 140 µmol/l OR calculated clearance > 60 ml/min (using either
Cockcroft-Gault formula or Modification of Diet in Renal Disease (MDRD) for >
65 years old),
- Direct and total bilirubin ≤ ULN.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
11. Accepting to use effective contraceptive measures or abstain from heterosexual
activity, for the course of the study and through 12 months after the last dose of
chemotherapy or being surgically sterile. All patients should seek advice regarding
cryoconservation of sperm prior treatment initiation because of the possibility of
infertility
12. Affiliation to a health insurance.
13. Signed and dated informed consent.
Non-exclusion criteria :
1. Extra-retroperitoneal metastasis on Computed tomography scan (CT scan).
2. Infection by Human Immunodeficiency Virus (HIV), or active infection with the
Hepatitis B or C virus.
3. History, within 2 years, of cancer other than seminoma, except for treated skin
cancer (basal cell).
4. Uncontrolled or severe cardiovascular pathology.
5. Uncontrolled or severe hepatic pathology.
6. Patient deprived of liberty or requiring tutorship or curatorship.
7. Psychological, physical, sociological, or geographical conditions that would limit
compliance with study protocol requirements (at the investigator's discretion).
8. Participation to another clinical trial, except for supportive care trials.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU Besançon
Address:
City:
Besançon
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Elodie KLAJER
Email:
elodie.klajer@gmail.com
Facility:
Name:
CHU Bordeaux
Address:
City:
Bordeaux
Country:
France
Status:
Recruiting
Contact:
Last name:
Marine GROSS-GOUPIL
Email:
marine.gross-goupil@chu-bordeaux.fr
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Country:
France
Status:
Recruiting
Contact:
Last name:
Florence JOLY
Email:
f.joly@baclesse.unicancer.fr
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Country:
France
Status:
Recruiting
Contact:
Last name:
Hakim MAHAMMEDI
Email:
hakim.mahammedi@clermont.unicancer.fr
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Country:
France
Status:
Recruiting
Contact:
Last name:
Thomas RYCKEWAERT
Email:
t-ryckewaert@o-lambret.fr
Investigator:
Last name:
Aurélien CARNOT
Email:
Sub-Investigator
Facility:
Name:
CHU de Limoges
Address:
City:
Limoges
Country:
France
Status:
Recruiting
Contact:
Last name:
Julia PESTRE MUNIER
Email:
julia.munier-pestre@chu-limoges.fr
Investigator:
Last name:
Valérie LE BRUN-LY
Email:
Sub-Investigator
Facility:
Name:
Centre Leon Bérard
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Aude FLECHON
Email:
aude.flechon@lyon.unicancer.fr
Investigator:
Last name:
Armelle VINCENEUX
Email:
Sub-Investigator
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Gwenaëlle GRAVIS
Email:
gravisg@ipc.unicancer.fr
Investigator:
Last name:
Slimane DERMECHE
Email:
Sub-Investigator
Investigator:
Last name:
Mathilde GUERIN
Email:
Sub-Investigator
Investigator:
Last name:
Cécile VICIER
Email:
Sub-Investigator
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Country:
France
Status:
Recruiting
Contact:
Last name:
Agnès DUCOULOMBIER
Email:
agnes.ducoulombier@nice.unicancer.fr
Investigator:
Last name:
Delphine BORCHIELLINI
Email:
Sub-Investigator
Facility:
Name:
Hôpital Saint Louis
Address:
City:
Paris
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Stéphane CULINE
Email:
stephane.culine@sls.aphp.fr
Investigator:
Last name:
Clément DUMONT
Email:
Sub-Investigator
Investigator:
Last name:
Tiphaine LAMBERT
Email:
Sub-Investigator
Facility:
Name:
ICO René Gauducheau
Address:
City:
Saint-Herblain
Country:
France
Status:
Recruiting
Contact:
Last name:
Emmanuelle BOMPAS
Email:
emmanuelle.bompas@ico.unicancer.fr
Investigator:
Last name:
Frédéric ROLLAND
Email:
Sub-Investigator
Facility:
Name:
Hôpital Foch
Address:
City:
Suresnes
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Christine ABRAHAM
Email:
c.abraham@hopital-foch.com
Facility:
Name:
Institut Universitaire de Cancer de Toulouse (IUCT-O)
Address:
City:
Toulouse
Country:
France
Status:
Recruiting
Contact:
Last name:
Christine CHEVREAU
Email:
chevreau.christine@iuct-oncopole.fr
Investigator:
Last name:
Thibaud VALENTIN
Email:
Sub-Investigator
Investigator:
Last name:
Loïc MOUREY
Email:
Sub-Investigator
Investigator:
Last name:
Damien POUESSEL
Email:
Sub-Investigator
Facility:
Name:
Institut de Cancérologie de Lorraine
Address:
City:
Vandœuvre-lès-Nancy
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Lionel GEOFFROIS
Email:
l.geoffrois@nancy.unicancer.fr
Investigator:
Last name:
Camille SIMON
Email:
Sub-Investigator
Investigator:
Last name:
Vincent MASSART
Email:
Sub-Investigator
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre BLANCHARD
Email:
pierre.blanchard@gustaveroussy.fr
Start date:
September 6, 2022
Completion date:
September 6, 2030
Lead sponsor:
Agency:
Centre Leon Berard
Agency class:
Other
Source:
Centre Leon Berard
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05529251
