Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma

NCT03937843 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: SAKK 01/182019-000514-11
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 19

Brief Summary

The trial investigates a stage-adapted (stage IIA or IIB) de-escalation of the standard treatments in the context of a multimodality treatment with chemo- and radiotherapy in seminoma patients. The goal is to safely de-escalate treatment while maintaining/enhancing efficacy, which is not a standard practice yet.

Conditions

Seminoma; Testicular Cancer

Keywords

Seminoma; Stage IIA/B seminoma; Radio-chemotherapy; Phase II trial; Testicular Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) at 3 years

  PFS is defined as the time from registration until one of the following events occurs: * Progressive disease or relapse, defined as progression according to the modified trial-specific version of RECIST 1.1 or a rising level of the tumor marker beta-hCG (beta human chorionic gonadotropin) over the ULN (Upper limit of normal), confirmed by a second measurement. Presence of non-seminoma germ cell tumor has to be excluded in the latter case * Death from any cause.

  From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 3 years after registration

Secondary Outcomes (9)

• Response rate (RR)

  at 3 months and 3 years after registration

• Progression free survival (PFS)

  From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 20 years after registration

• Time to progression (TTP)

  From the date of registration until the date of progressive disease, relapse or death due to progression, whichever occurs first, assessed up to 20 years after registration

• Overall Survival (OS)

  From the date of registration until the date of death from any cause, assessed up to 20 years after registration

• Seminoma-specific survival

  From the date of registration until the date of death due to seminoma, assessed up to 20 years after registration

Study Arms (1)

Arm with 2 cohorts

EXPERIMENTAL

Cohort 1: Primary stage IIA and recurrent stage IIA seminoma after active surveillance for stage I: * Within 7 days after registration, the patients will receive one infusion of carboplatin AUC (Area under the curve) 7 at day 1 of trial treatment, followed 3 weeks later by 12 x 2 Gy involved-node radiation therapy (RT). RT should ideally start on day 22 (range: day 19-25) from the date of carboplatin administration, preferably on a Monday. Cohort 2: Primary stage IIB and recurrent stage IIB seminoma after active surveillance for stage I OR stage IIA/B seminoma after adjuvant carboplatin or radiotherapy for stage I: * Within 7 days after registration, the patients will receive one cycle of etoposide 100 mg/m2/d + cisplatin 20 mg/m2/d at days 1 to 5 of trial treatment, followed 3 weeks later by 15 x 2 Gy involved-node radiation therapy. RT should ideally start on day 22 (range: day 19-25) from the date of chemotherapy start, preferably on a Monday.

Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide

Interventions

Carboplatin DRUG

Patients in cohort 1 will receive a 60-minute i.v. infusion of carboplatin AUC 7 at day 1 of treatment.

Arm with 2 cohorts

Cisplatin DRUG

Patients in cohort 2 will receive on day 1 to day 5: * a 60-minutes i.v. infusion of etoposide 100mg/m2 per day followed by * a 60-120 minutes i.v. infusion of cisplatin 20mg/m2 per day.

Arm with 2 cohorts

Etoposide DRUG

Patients in cohort 2 will receive on day 1 to day 5: * a 60-minutes i.v. infusion of etoposide 100mg/m2 per day followed by * a 60-120 minutes i.v. infusion of cisplatin 20mg/m2 per day.

Arm with 2 cohorts

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to ICH/GCP (International Council on Harmonization/Good Clinical Practice) regulations before registration and prior to any trial specific procedures
• Histologically confirmed classical seminoma treated with primary inguinal orchidectomy or partial orchidectomy
• Patients with a seminoma stage IIA or IIB, either newly diagnosed or recurrent after primary active surveillance, adjuvant carboplatin or radiotherapy for stage I disease. The tumor stage is pT1-4 cN1-2 cM0 according to UICC TNM 8th edition 2016. Patients with a recurrent seminoma stage IIA or IIB are only eligible in case of progression under active surveillance or recurrence after adjuvant carboplatin or radiotherapy for stage I disease
• Stage IIA, in patients with equivocal lymph node enlargement, needs to be confirmed with a repeated CT/MRI scan of the abdomen (suggested timeframe: 4 weeks after the previous scan) in order to rule out false positive lymph node enlargement.
• Patients with a prior malignancy treated with curative intention are eligible if all treatment of that malignancy was completed at least 5 years before registration and the patient has no evidence of disease at registration. Less than 5 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence. Patients with a germ cell neoplasia in situ (GCNIS) or contralateral localized treated seminoma are eligible
• Diagnostic CT or MRI or FDG-PET-CT of the chest, abdomen and pelvis within 28 days prior to registration, showing stage IIA/B disease. I.v. contrast medium has to be administered
• Age ≥ 18 years
• WHO performance status 0-2
• Baseline PRO questionnaires have been completed
• Adequate bone marrow function: neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 100x 109/L
• Adequate renal function: creatinine clearance ≥ 60 ml/min calculated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
• Patient agrees to use highly effective contraception and not to donate sperm or to father a child during trial treatment and during 12 months thereafter. Patient has been proposed sperm conservation.

You may not qualify if:

• Any other histological component than seminoma
• Elevated levels of Alpha-1-Fetoprotein AFP (≥ 2x ULN)
• Involved nodes (metastatic) in previously irradiated localizations in the abdomen or pelvis
• Any anti-cancer therapy after primary tumor resection in patients presenting with primary stage IIA/B seminoma
• Any serious underlying medical condition (i.e. current renal insufficiency, severe hepatic insufficiency, severe bone marrow dysfunction, tumor bleeding, major hearing defects) or serious co-morbidity which could impair the ability of the patient to participate in the trial (according to investigator's judgment)
• Any treatment in a clinical trial within 28 days prior to registration
• Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information or contraindicated for use with radiotherapy
• Known hypersensitivity to trial drugs or to any component of the trial drugs
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
• Patient who is dependent on the sponsor or the investigators according to ICH/GCP E6(R2), guideline
• Patient who has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities according to § 40a (2) AMG.

Sponsors & Collaborators

• Swiss Cancer Institute: lead
• German Testicular Cancer Study Group: collaborator

Study Sites (19)

Rotkreuzklinikum München

München, München, 80364, Germany

Location

Vivantes Klinikum Am Urban

Berlin, 10967, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Evang. Kliniken Essen-Mitte

Essen, 45136, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

ASKLEPIOS Kliniken

Hamburg, 22763, Germany

Location

RKH Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, CH-6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, CH-1011, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hopital de Sion

Sion, 1951, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Seminoma; Testicular Neoplasms

Interventions

Carboplatin; Cisplatin; Etoposide

Condition Hierarchy (Ancestors)

Germinoma; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Alexandros Papachristofilou, MD

  Universitätsspital Basel

  STUDY CHAIR

Study Design

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

Model Details: A multicenter, open label phase II trial with two cohorts

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 6, 2019
• Study Start: July 29, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2046
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

DE (9); CH (10)