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

Last updated: January 24, 2024
Sponsor: Centre Leon Berard
Overall Status: Active - Recruiting

Phase

2

Condition

Germ Cell Tumors

Testicular Cancer

Treatment

Radiotherapy boost

3 cycles of EP

Carboplatin AUC7

Clinical Study ID

NCT05529251
EDEN (ET21-344)
  • Ages > 18
  • Male

Study 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.

Eligibility Criteria

Inclusion

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.

  1. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

  2. 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

  3. Affiliation to a health insurance.

  4. 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.

Study Design

Total Participants: 90
Treatment Group(s): 3
Primary Treatment: Radiotherapy boost
Phase: 2
Study Start date:
September 06, 2022
Estimated Completion Date:
September 06, 2030

Study 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.

Connect with a study center

  • CHU Besançon

    Besançon,
    France

    Site Not Available

  • CHU Bordeaux

    Bordeaux,
    France

    Active - Recruiting

  • Centre François Baclesse

    Caen,
    France

    Active - Recruiting

  • Centre Jean Perrin

    Clermont-Ferrand,
    France

    Active - Recruiting

  • Centre Oscar Lambret

    Lille,
    France

    Active - Recruiting

  • CHU de Limoges

    Limoges,
    France

    Active - Recruiting

  • Centre Leon Bérard

    Lyon,
    France

    Active - Recruiting

  • Institut Paoli Calmettes

    Marseille,
    France

    Active - Recruiting

  • Centre Antoine Lacassagne

    Nice,
    France

    Active - Recruiting

  • Hôpital Saint Louis

    Paris,
    France

    Site Not Available

  • ICO René Gauducheau

    Saint-Herblain,
    France

    Active - Recruiting

  • Hôpital Foch

    Suresnes,
    France

    Site Not Available

  • Institut Universitaire de Cancer de Toulouse (IUCT-O)

    Toulouse,
    France

    Active - Recruiting

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy,
    France

    Site Not Available

  • Institut Gustave Roussy

    Villejuif,
    France

    Active - Recruiting

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