PRIMETEST II - Clinical Stage II A/B Seminoma Treated With RA-RPLND

PRIMETEST II - Phase II Trial to Prospectively Test New Predictors for Recurrence in Patients With Clinical Stage II A/B Seminoma Treated With RA-RPLND

PRIMETEST II is an interventional study involving low-volume metastatic seminoma. It explores a novel approach using robot-assisted primary retroperitoneal lymph node dissection, aiming to reduce long-term side effects and improve quality of life. By identifying factors predicting cancer recurrence, the study hopes to tailor treatments for better outcomes. The approach could potentially spare patients from chemotherapy induced long-term side effects while maintaining excellent survival rates, presenting a promising shift in testicular cancer care for this specific patient group.

Study Overview

• Status: Recruiting
• Conditions: Seminoma
• Intervention / Treatment: Procedure: Robot-assisted retroperitoneal lymph node dissection; Drug: Adjuvant therapy with one cycle of cisplatin, etoposide and bleomycin

Detailed Description

Testicular cancer stands as the most prevalent cancer among young men, boasting a highly favorable prognosis characterized by almost unaltered long-term survival even in advanced stages. However, traditional treatments like chemotherapy and radiation are linked to significant long-term toxicity and increased rates of secondary malignancies. Particularly, late toxicities, mainly cardiovascular, substantially diminish overall survival by approximately 6-7 years. To circumvent unnecessary acute and long-term toxicities associated with radiation or chemotherapy, it's crucial to explore alternative therapeutic avenues through personalized, less toxic approaches.

Building upon the hypothesis-generating PRIMETEST I study, PRIMETEST II is a single-arm, non-randomized prospective study. It aims to explore novel and personalized predictive parameters for recurrence following a robot-assisted primary retroperitoneal lymph node dissection (pRA-RPLND) in patients with clinical stage IIA/B seminoma (involving low-volume metastatic disease up to 5 cm). These patients represent a rare subgroup among testicular cancer patients, making a randomized comparison of treatment options impractical due to their low prevalence. The overarching goal is to reduce long-term toxicity in this young cohort of cancer patients and enhance their quality of life through personalized clinical and molecular predictions.

PRIMETEST I has indicated that pRA-RPLND in patients with clinical stage IIA/B seminoma led to a 70% recurrence-free survival at 32 months' follow-up. These findings suggest that pRA-RPLND could serve as an alternative to standard therapies (chemotherapy, radiotherapy) for a highly selective group of patients, effectively preventing excessive toxicity. PRIMETEST I has already identified several potential factors that predict which patients are more likely to benefit from surgical therapy alone.

In the novel prospective setting of PRIMETEST II, the study tests the identified predictive factors for recurrence. Patients exhibiting presumably low-risk features (about 70% of patients) will continue with surgery alone. Those with a presumed higher risk of recurrence will undergo robot-assisted surgery and have the option of receiving adjuvant treatment (one cycle of cisplatin, etoposide, and bleomycin). The primary endpoint is a three-year recurrence-free survival, estimated to exceed 90%. Additional objectives include exploring new predictors of recurrence at both molecular and clinical levels by analyzing serum and tissue samples from the primary tumor and metastases.

This innovative approach anticipates that 70% of patients will avoid long-term toxicity and experience excellent recurrence-free survival rates comparable to standard chemotherapy or radiation therapy.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yue Che; Phone Number: 00492118118110; Email: yue.che@med.uni-duesseldorf.de

Study Locations

• Germany
  • Düsseldorf, Germany
    • Recruiting
    • University Hospital of Duesseldorf
    • Contact: Peter Albers; Email: peter.albers@med.uni-duesseldorf.de
    • Contact: Yue Che; Email: yue.che@med.uni-duesseldorf.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed pure seminomatous testicular germ cell tumor
• Presence of iliac or retroperitoneal lymph node metastasis detected in contrast-enhanced CT or MRI, classified as local or unilaterally regional
• Maximum extent of lymph node metastasis (LN-M) singular or multiple, with a maximum size of 5 cm in transverse CT diameter (UICC IIB)
• Patients with an elevation in HCG after orchiectomy at the time of staging examination can be included if the directly preoperatively determined HCG does not exceed 5 IU/L.

Patients can be included in the following scenarios:

• Initial diagnosis of a tumor in UICC stage IIA/IIB
• Recurrence of a tumor in clinical stage (CS) I under active surveillance
• Recurrence of a CS I tumor after adjuvant therapy with carboplatin mono

Exclusion Criteria:

• LN-M with a transverse diameter >5 cm in CT (UICC IIC)
• Other metastases than LN-M (UICC III)
• The patient received a different chemotherapy than described above
• The patient underwent retroperitoneal radiotherapy
• The patient is in a reduced general condition or has a life-threatening illness
• The patient has a psychiatric illness
• Evidence of non-seminomatous germ cell tumor components in the RPLND histology
• Complete resection cannot be ensured due to previous surgeries
• In the "high risk" group: Contraindications to cisplatin, etoposide, or bleomycin (severe liver insufficiency, severe kidney insufficiency, severe lung insufficiency, hypersensitivity, severe bone marrow depression, profound hearing impairments)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low risk; Criteria for "low risk": Absence of "high risk" criteria; Previous carboplatin therapy post orchiectomy; Exclusion of malignancy in the RPLND histology	Procedure: Robot-assisted retroperitoneal lymph node dissection; Robot-assisted, if possibe ipsilateral nerve-sparing, retroperitoneal lymph node dissection and metastasis resection in a unilateral dissection field ("template")
Experimental: High risk; Criteria for "high risk": Clinical stage II at initial diagnosis; Primary tumor > 4 cm; Infiltration of the "rete testis" in the primary tumor	Procedure: Robot-assisted retroperitoneal lymph node dissection; Robot-assisted, if possibe ipsilateral nerve-sparing, retroperitoneal lymph node dissection and metastasis resection in a unilateral dissection field ("template"); Drug: Adjuvant therapy with one cycle of cisplatin, etoposide and bleomycin; The patient is given the option for an adjuvant therapy with one cycle of cisplatin, etoposide and bleomycin two to four weeks after RA-RPLND

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		at least 5 years
Time to progression		from intervention to progression assessed up to 5 years
Complications	Intraoperative Adverse Incident Classification (EAUiaiC) by the European Association of Urology ad hoc Complications Guidelines Panel, Clavien-Dindo	intra- and perioperative
Quality of life	EORTC QLQ-C30 and QLQ-TC26	baseline and yearly, up to 5 years
Mental health	Questionnaire	baseline and yearly, up to 5 years
Rate of retrograde ejaculation		postoperative assessment yearly, up to 5 years
Validation of microRNA-371	Measurements of the biomarker microRNA-371	Day before surgery, day 3-5 after surgery and in case of adjuvant therapy 3 days from last drug application
Analysis of molecular characteristics	Measurements still not specified	after study recruitment completion

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Yue Che, University Hospital of Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: seminoma; low volume metastases; clinical stage IIA/B
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Germinoma; Seminoma; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Glycoconjugates; Glycopeptides; Etoposide; Bleomycin
• Other Study ID Numbers: 2022-2256

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No