RecruitingPhase 2NCT05529251

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

Prospective Therapeutic De-escalation and miRNA-M371 Biomarker Evaluation Phase II Study for Stage IIa/IIb < 3 cm Seminomas


Sponsor

Centre Leon Berard

Enrollment

90 participants

Start Date

Sep 6, 2022

Study Type

INTERVENTIONAL

Conditions

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

Sex: MALEMin Age: 18 Years

Inclusion Criteria17

  • 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
  • Affiliation to a health insurance.
  • Signed and dated informed consent.

Exclusion Criteria8

  • 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.

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Interventions

RADIATIONRadiotherapy boost

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

DRUGCarboplatin AUC7

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

DRUG3 cycles of EP

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


Locations(15)

CHU Besançon

Besançon, France

CHU Bordeaux

Bordeaux, France

Centre François Baclesse

Caen, France

Centre Jean Perrin

Clermont-Ferrand, France

Centre Oscar Lambret

Lille, France

CHU de Limoges

Limoges, France

Centre Leon Bérard

Lyon, France

Institut Paoli Calmettes

Marseille, France

Centre Antoine Lacassagne

Nice, France

Hôpital Saint Louis

Paris, France

ICO René Gauducheau

Saint-Herblain, France

Hôpital Foch

Suresnes, France

Institut Universitaire de Cancer de Toulouse (IUCT-O)

Toulouse, France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Institut Gustave Roussy

Villejuif, France

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