Phase II Multicenter Trial of Reduced Intensity Radiochemotherapy with Carboplatin, Etoposide, and Cisplatin in Stage IIA/B Seminoma
- Trial ID
- 2023-509663-24-00
- Protocol
- SAKK 01/18
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to investigate the **efficacy** of a stage-adapted treatment regimen in patients with Stage IIA/B seminoma, building on preliminary experience from the SAKK 01/10 trial. This is clinically relevant as it aims to optimize treatment strategies for this specific stage of seminoma, potentially improving patient outcomes and minimizing treatment-related adverse effects.
Secondary objectives include evaluating various clinical outcomes and safety parameters associated with the treatment regimen. These include:
- Response Rate
- Progression-Free Survival (PFS)
- Time to Progression (TTP)
- Overall Survival (OS)
- Seminoma-specific survival
- Time to distant metastasis
- Time to next treatment
- Localization and method of detection of progression
- Adverse Events (AE) and late AE
- Incidence of second tumors
- Development of metabolic syndrome
- Development of hypogonadism
These secondary objectives are crucial for understanding the broader impact of the treatment regimen on patient health and long-term outcomes.
Participants
The clinical trial involves a total of **85 participants** diagnosed with **Stage IIA/B seminoma**, a type of testicular cancer. The study population consists exclusively of male subjects, as indicated by the nature of the condition being investigated. Participants are adults aged 18 years and older, with a **WHO performance status** ranging from 0 to 2, indicating they are in relatively good health and capable of self-care. The selection process for the trial population was based on specific inclusion criteria, including adequate renal and bone marrow function, and a histologically confirmed diagnosis of classical seminoma treated with primary inguinal or partial orchidectomy. Participants were required to provide written informed consent and agree to use highly effective contraception during and after the trial. Lifestyle considerations such as diet and physical activity were not specified as part of the selection criteria. The trial does not include a vulnerable population, and the participants are not selected based on any specific lifestyle habits. The study aims to evaluate the efficacy of a stage-adapted treatment regimen for this condition.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a stage-adapted treatment regimen for patients with **Stage IIA/B seminoma**. This is a multicenter, open-label, phase II trial involving two cohorts. The trial employs a randomized, controlled methodology to ensure the reliability of the results. The estimated duration of the trial is from September 1, 2020, to March 31, 2045, allowing for comprehensive data collection and analysis over an extended period.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as adequate renal and bone marrow function, and a histologically confirmed diagnosis of classical seminoma. Following the screening, participants will be randomized into treatment groups and will receive the investigational products, which include **carboplatin**, **etoposide**, and **cisplatin**, all administered as solutions for infusion. The treatment period varies, with a maximum of 5 days for some products.
Follow-up visits will be scheduled to monitor the participants' response to treatment and to assess any adverse effects. These visits are crucial for evaluating the primary endpoint of progression-free survival at 3 years, as well as secondary endpoints such as response rate, overall survival, and time to progression. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to gather comprehensive data on the treatment's efficacy and safety.
The expected length of participant involvement is contingent upon the treatment regimen and follow-up schedule, with the possibility of early termination if specific conditions arise, such as significant adverse reactions or disease progression. Participants are required to adhere to trial protocols, including the use of effective contraception and compliance with follow-up assessments, to ensure the integrity of the trial data.
Treatment
The clinical trial involves the administration of **Carboplatin**, marketed as Carboplat Onkovis 10 mg/ml, which is a **solution for infusion**. This experimental medication is provided as a concentrate for the preparation of an infusion solution. The active substance, carboplatin, is of chemical origin. The maximum daily dose is 60 minutes of infusion, with a total treatment period of 1 day. The administration route is intravenous infusion, and the product is manufactured by ONKOVIS GMBH.
Another experimental medication used in the trial is **Etoposide**, marketed as Etomedac 20 mg/ml. This medication is also a **solution for infusion** and is provided as a concentrate for infusion preparation. The active substance, etoposide, is chemically derived. The maximum daily dose is 100 mg/m², with a total dose of 500 mg/m² over a treatment period of 5 days. The route of administration is intravenous infusion, and the product is manufactured by MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL).
The trial also includes the administration of **Cisplatin**, marketed as Cisplatin NeoCorp 1 mg/ml. This medication is a **solution for infusion** and is provided as a concentrate for infusion preparation. The active substance, cisplatin, is of chemical origin. The maximum daily dose is 20 mg/m², with a total dose of 100 mg/m² over a treatment period of 5 days. The administration route is intravenous infusion, and the product is manufactured by HEXAL AG.
All medications are administered as part of a stage-adapted treatment regimen for Stage IIA/B seminoma, with the primary objective of investigating the efficacy of this regimen. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.
Efficacy
The efficacy of the treatment regimen in the clinical trial for stage IIA/B seminoma will be assessed using several key endpoints. The primary endpoint is **Progression Free Survival (PFS)** at 3 years. Secondary endpoints include Response Rate (RR), overall PFS, Time to Progression (TTP), Overall Survival (OS), seminoma-specific survival, Time to Distant Metastasis, Time to Next Treatment, Localization of Progression, and Method of Detection of Progression. These endpoints will provide a comprehensive evaluation of the treatment's effectiveness in managing the disease.
Data collection for these endpoints will be conducted through diagnostic imaging techniques such as CT, MRI, or FDG-PET-CT scans of the chest, abdomen, and pelvis, which are required within 28 days prior to registration to confirm stage IIA/B disease. The trial will follow a multicenter, open-label phase II design, with efficacy assessments scheduled at various timepoints throughout the study duration. The trial aims to gather robust data to determine the efficacy of the stage-adapted treatment regimen based on previous experiences from SAKK 01/10.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent according to ICH/GCP 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 10^9/L, platelet count ≥ 100x 10^9/L
- Adequate renal function: creatinine clearance ≥ 60 ml/min calculated according to the CKD-EPI 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
- Additional German specific exclusion criterion - not to be considered for Swiss patients: Patient who is dependent on the sponsor or the investigators according to ICH/GCP E6(R2) guideline
- Additional German specific exclusion criterion - not to be considered for Swiss patients: 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Sept 2020 | 95 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Carboplat onkovis 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | CONCENTRATE FOR SOLUTION FOR INFUSION | 60 | 1 | PRD1808013 |
Etomedac 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | CONCENTRATE FOR SOLUTION FOR INFUSION | 100 | 5 | PRD577121 |
Cisplatin NeoCorp 1 mg/ml - Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | CONCENTRATE FOR SOLUTION FOR INFUSION | 20 | 5 | PRD759858 |