De-escalation Study for Stage IIa/IIb < 3 cm Seminoma

NCT05529251 | Recruiting Phase 2 DMC

• 1 other identifier: EDEN (ET21-344)
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Seminoma; Stage II

Keywords

De-escalation; Chemotherapy; Radiotherapy; Carboplatin; Etoposide; Cisplatine; Micro-RNA-M371; PET scan; Overall survival; Biomarker; Efficacy; Progression free rate; Safety; Quality of life

Outcome Measures

Primary Outcomes (1)

• PFR-36M

  Progression-free rate at 36 months The PFR-36M is assumed to be a random variable following a binomial distribution Bin (n, p) where n is the sample size and p is the true underlying PFR-36M. Conclusions and inferences will be conducted on p. The prior distribution of p (representing the knowledge of the progression-free rate probability prior to observing the data) will be pre-specified. In the absence of a strong idea about the PFR-36M to be observed, a non-informative prior distribution Beta (1,1) will be considered. Pr\[PFR-36M ≥ 80%\] will be expressed in each arm, associated with its 95% credibility interval. A treatment arm will be considered a positive sign for efficacy of de-escalation if there is a high probability that PFR-36M will be higher or equal to 80%: Pr\[PFR-36M ≥ 80%\] ≥ 90%. It means that if most of the distribution (90% of it) falls to the right hand side of 80%, it indicates that it is very likely that the effect is at least 80%

  Up to 36 months after inclusion

Secondary Outcomes (5)

• miRNA-M371

  Up to 5 years

• Association of PET scan results and miRNA-M371 rate

  Up to 5 years

• Overall survival (OS)

  Up to 3 years

• Quality of life (QoL)

  Up to 20 months

• Tolerance to treatment

  Up 5 years

Study Arms (4)

ARM A

EXPERIMENTAL

RADIOTHERAPY boost 20 to 30 Gy on lymph nodes

Radiation: Radiotherapy boost

ARM B

EXPERIMENTAL

One cycle of CARBOPLATIN AUC7

Drug: Carboplatin AUC7

ARM C

OTHER

3 cycles of ETOPOSIDE and CISPLATIN

Drug: 3 cycles of EP

OBSERVATIONAL COHORT

NO INTERVENTION

STANDARD RADIOTHERAPY on lymph nodes

Interventions

Radiotherapy boost RADIATION

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 A

Carboplatin AUC7 DRUG

Carboplatin at dose (mg) = AUC7 (mg/ml x min) x (DFG ml/min + 25)

ARM B

3 cycles of EP DRUG

3 Cycles of EP chemotherapy, administred every 3 weeks following standard practice

ARM C

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years on the day of signing informed consent.
• Primary testicular seminomatous germ cell tumor.
• Stage IIa/IIb \< 3 cm in largest diameter seminoma, histologically proved after orchiectomy.
• Confirmation of a progressive disease (positive PET scan or increase of lymph nodes size by two successive CT scan).
• Good prognosis according to IGCCCG and LDH \< 2.5 x Upper Limit of Normal (ULN).
• Normal alpha-fetoprotein (AFP) before and after orchiectomy.
• No prior treatment with radiotherapy or chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
• 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.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• 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

You may not qualify if:

• Extra-retroperitoneal metastasis on Computed tomography scan (CT scan).
• Infection by Human Immunodeficiency Virus (HIV), or active infection with the Hepatitis B or C virus.
• History, within 2 years, of cancer other than seminoma, except for treated skin cancer (basal cell).
• Uncontrolled or severe cardiovascular pathology.
• Uncontrolled or severe hepatic pathology.
• Patient deprived of liberty or requiring tutorship or curatorship.
• Psychological, physical, sociological, or geographical conditions that would limit compliance with study protocol requirements (at the investigator's discretion).
• Participation to another clinical trial, except for supportive care trials.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (15)

CHU Besançon

Besançon, France

NOT YET RECRUITING

CHU Bordeaux

Bordeaux, France

RECRUITING

Centre François Baclesse

Caen, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Centre Oscar Lambret

Lille, France

RECRUITING

CHU de Limoges

Limoges, France

RECRUITING

Centre Leon Bérard

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Hôpital Saint Louis

Paris, France

NOT YET RECRUITING

ICO René Gauducheau

Saint-Herblain, France

RECRUITING

Hôpital Foch

Suresnes, France

NOT YET RECRUITING

Institut Universitaire de Cancer de Toulouse (IUCT-O)

Toulouse, France

RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Seminoma

Condition Hierarchy (Ancestors)

Germinoma; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Aude FLECHON, Dr

  Centre Leon Berard (Lyon, France)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen BLANC

CONTACT

+33 4 78 78 29 67; ellen.blanc@lyon.unicancer.fr

Aude FLECHON, Dr

CONTACT

+ 33 4 78 78 26 43; aude.flechon@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * 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

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: September 7, 2022
• Study Start: September 6, 2022
• Primary Completion: September 6, 2025
• Study Completion (Estimated): September 6, 2030
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

FR (15)