Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma

NCT ID: NCT03937843

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-29
• Study Completion Date: 2046-12-31

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.

Detailed Description

Therapy de-escalation in stage IIA/B seminoma represents an unmet need in clinical practice; efficacy of modern standard of care therapies for these patients is high and only a few patients show disease recurrence but short- and long-term toxicities are a major concern. The magnitude of long-term toxicities is often associated with the intensity of the prescribed treatment modality. A higher cumulative dose of chemotherapy agents and radiation dose has been linked to a sharp increase in long-term sequelae. Combining treatment modalities and diversifying toxicity may thus provide an opportunity to limit long-term treatment sequelae.

In this trial carboplatin, cisplatin and etoposide are the Investigational Medicine Products (IMPs). They are all medications with a marketing authorization for several solid tumor types and are standard practice in the treatment of testicular cancer in Switzerland and in the European Union (EU).

Radiotherapy is also a standard therapy in this indication.

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

The SAKK 01/18 trial is designed with the aim to answer these three questions:

• Can the dose of involved-node radiotherapy be safely reduced in the context of multimodality treatment with chemo- and radiotherapy?
• Can a more potent chemotherapy in the form of cisplatin/etoposide reduce the rate of distant failure in comparison to carboplatin?
• Can a combination of cisplatin/etoposide and involved-node radiotherapy pose a potent treatment regime for patients with recurrence after adjuvant carboplatin or radiotherapy for stage I seminoma? Furthermore, as active surveillance is becoming standard of care in stage I seminoma, it is projected that the amount of patients in need of treatment with stage IIA/B disease will rise, due to more patients developing disease progression during active surveillance.

The trial design, trial treatment and trial specifics are a consensus among the Swiss Urogenital Tumors Project Group and the Swiss Radio-oncology Section from the Swiss Group for Clinical Cancer Research (SAKK) and the German Testicular Cancer Study Group (GTCSG).

Conditions

Seminoma; Testicular Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm with 2 cohorts

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.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

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

Cisplatin

Intervention Type: 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.

Etoposide

Intervention Type: 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.

Interventions

Carboplatin

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

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Etoposide

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

German Testicular Cancer Study Group

OTHER

Sponsor Role: collaborator

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandros Papachristofilou, MD

Role: STUDY_CHAIR

Universitätsspital Basel

Locations

Rotkreuzklinikum München

München, München, Germany

Vivantes Klinikum Am Urban

Berlin, , Germany

Helios Klinikum Berlin-Buch

Berlin, , Germany

Evang. Kliniken Essen-Mitte

Essen, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

ASKLEPIOS Kliniken

Hamburg, , Germany

RKH Klinikum Ludwigsburg

Ludwigsburg, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopital de Sion

Sion, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

UniversitätsSpital Zürich

Zurich, , Switzerland

Countries

Germany; Switzerland

Other Identifiers

2019-000514-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAKK 01/18

Identifier Type: -

Identifier Source: org_study_id