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

NCT ID: NCT05529251

Last Updated: 2024-01-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-06

Study Completion Date

2030-09-06

Brief Summary

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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

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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.

Conditions

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Seminoma Stage II

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

* 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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARM A

RADIOTHERAPY boost 20 to 30 Gy on lymph nodes

Group Type EXPERIMENTAL

Radiotherapy boost

Intervention Type 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 B

One cycle of CARBOPLATIN AUC7

Group Type EXPERIMENTAL

Carboplatin AUC7

Intervention Type DRUG

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

ARM C

3 cycles of ETOPOSIDE and CISPLATIN

Group Type OTHER

3 cycles of EP

Intervention Type DRUG

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

OBSERVATIONAL COHORT

STANDARD RADIOTHERAPY on lymph nodes

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Radiotherapy 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

Intervention Type RADIATION

Carboplatin AUC7

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

Intervention Type DRUG

3 cycles of EP

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

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Centre Leon Berard

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aude FLECHON, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard (Lyon, France)

Locations

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CHU Besançon

Besançon, , France

Site Status NOT_YET_RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

Centre François Baclesse

Caen, , France

Site Status RECRUITING

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

CHU de Limoges

Limoges, , France

Site Status RECRUITING

Centre Leon Bérard

Lyon, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status NOT_YET_RECRUITING

ICO René Gauducheau

Saint-Herblain, , France

Site Status RECRUITING

Hôpital Foch

Suresnes, , France

Site Status NOT_YET_RECRUITING

Institut Universitaire de Cancer de Toulouse (IUCT-O)

Toulouse, , France

Site Status RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status NOT_YET_RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Ellen BLANC

Role: CONTACT

+33 4 78 78 29 67

Aude FLECHON, Dr

Role: CONTACT

+ 33 4 78 78 26 43

Facility Contacts

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Elodie KLAJER

Role: primary

Marine GROSS-GOUPIL

Role: primary

Florence JOLY

Role: primary

Hakim MAHAMMEDI

Role: primary

Thomas RYCKEWAERT

Role: primary

Julia PESTRE MUNIER

Role: primary

Aude FLECHON

Role: primary

Gwenaëlle GRAVIS

Role: primary

Agnès DUCOULOMBIER

Role: primary

Stéphane CULINE

Role: primary

Emmanuelle BOMPAS

Role: primary

Christine ABRAHAM

Role: primary

Christine CHEVREAU

Role: primary

Lionel GEOFFROIS

Role: primary

Pierre BLANCHARD

Role: primary

Other Identifiers

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EDEN (ET21-344)

Identifier Type: -

Identifier Source: org_study_id

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