Oral etoposide versus observation after high-dose chemotherapy for relapsed germ cell tumors

Randomized Phase 2 Trial of Maintenance Oral Etoposide or Observation Following High-dose Chemotherapy for Relapsed Metastatic Germ-Cell Tumor

This study is testing if taking daily oral etoposide after high-dose chemotherapy can help people with relapsed germ cell tumors do better than just watching and waiting.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Indiana University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Indianapolis, Indiana)
• Trial ID: NCT04804007 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of maintenance oral etoposide compared to observation in patients with relapsed germ cell tumors (GCT) who have recently undergone high-dose chemotherapy and peripheral-blood stem-cell transplant. Participants will be randomly assigned to receive either daily oral etoposide or no additional treatment after completing their initial salvage therapy. The study aims to determine if maintenance therapy can improve outcomes for these patients. The trial is open-label, meaning both the researchers and participants will know which treatment is being administered.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed non-seminomatous germ cell tumors who have completed high-dose chemotherapy and stem cell transplant within the last 16 weeks.

Not a fit: Patients who have not experienced a relapse after first-line chemotherapy or those with significant adverse events from prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve survival rates and reduce the risk of relapse in patients with relapsed germ cell tumors.

How similar studies have performed: While there have been studies on maintenance therapies in various cancers, this specific approach with oral etoposide for relapsed germ cell tumors is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent and HIPAA authorization for release of personal health information
2. Age ≥ 18 years at the time of consent
3. Histological or serological evidence of non-seminomatous GCT
4. Relapsed disease after first-line cisplatin-based combination chemotherapy
5. Completed salvage treatment with HDCT and PBSCT for 2 tandem cycles per Institutional Guidelines
6. HDCT must have been used as the initial salvage chemotherapy regimen (2nd line therapy) 6.1. Note: 1 or 2 cycles of standard course regimens prior to HDCT are acceptable (regimens include VeIP \[vinblastine+ifosfmaide+cisplatin\] or TIP \[paclitaxel+ifosfamide+cisplatin\] or PVB \[cisplatin+vinblastine+bleomycin\]
7. Normal or declining tumor markers (AFP and hCG) at time of screening
8. Adverse events from prior therapy recovered to CTCAE v5.0 grade ≤ 2 at time of registration
9. Women with ovarian germ cell tumors are eligible
10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 28 days of study registration
11. Last dose of HDCT must be ≤16 weeks from study registration
12. Adequate organ function lab values obtained within 28 days prior to study registration System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,000 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥8 g/dL Renal Serum creatinine \<2mg/dL Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN

    AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
    * 5 X ULN for subjects with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
13. If a female of childbearing potential, a negative urine pregnancy test within 28 days prior to receiving the first dose of study drug.

    o Non-childbearing potential is defined as (by other than medical reasons):
    * ≥ 45 years of age and has not had menses for \>2 years
    * Amenorrheic for \< 2 years without a hysterectomy and/or oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation
    * Post hysterectomy or oophorectomy. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound.
14. For female patients of childbearing potential and male patients, agreement (by patient and/or partner) to use two forms of highly effective contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) starting with the first dose of study therapy and to continue its use for 30 days after the last dose of study therapy, or abstain from heterosexual activity.

Exclusion Criteria:

1. Relapsed pure seminoma
2. Rising tumor markers (AFP and hCG) at time of screening
3. Patients who completed 2nd cycle of HDCT (time since last dose of HDCT) \>16 weeks ago
4. Treatment with any investigational agent within 28 days prior to study registration
5. Other active malignancy requiring treatment in past 12 months
6. History of psychiatric illness or social situations that would limit compliance with study requirements
7. Active infection requiring systemic therapy
8. Previous hypersensitivity to etoposide which did not recover with supportive care
9. Pregnancy, lactation, or breastfeeding
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Where this trial is running

Indianapolis, Indiana

• Indiana University Melvin & Bren Simon Cancer Center — Indianapolis, Indiana, United States (Recruiting)

Study contacts

• Principal investigator: Nabil Adra, MD — Indiana University
• Study coordinator: Christin Snow, RN

Conditions Germ Cell Tumor; Non-seminomatous Germ Cell Tumor; Ovarian Germ Cell Tumor