Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT

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

This is an open label randomized phase II trial of maintenance oral etoposide vs. observation in patinets with relapsed GCT treated with high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplant (PBSCT).

Study Overview

• Status: Recruiting
• Conditions: Ovarian Germ Cell Tumor; Germ Cell Tumor; Non-seminomatous Germ Cell Tumor
• Intervention / Treatment: Drug: Etoposide

Detailed Description

This is a randomized phase 2 trial of maintenance etoposide versus observation following HDCT+PBSCT for relapsed GCT. Patients who completed HDCT+PBSCT within the past 16 weeks will enroll and randomize in 1:1 fashion to maintenance daily oral etoposide 50mg vs. observation only.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christin Snow, RN; Phone Number: 317-274-5830; Email: chsnow@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin & Bren Simon Cancer Center
      • Principal Investigator: Nabil Adra, MD
      • Contact: Christin Snow, RN; Phone Number: 317-274-5830; Email: chsnow@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maintenance Oral Etoposide; Maintenance daily oral Etoposide.	Drug: Etoposide; etoposide will be provided with prescription for etoposide 50mg orally daily for 21 days out of 28 day cycles. Cycles will be repeated every 4 weeks for a total of 3 cycles.
No Intervention: Observation; If randomized to Observation, subjects will jump to follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month Progression Free Survival	Investigator determination of tumor progression (clinical, radiographic, tumor markers including AFP and hCG)	time from the date of randomization to the date of disease relapse or death (i.e. up to 1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month Overall Survival		Time of registration to death from any cause (i.e. up to 1 year)
Assess toxicity and tolerability of maintenance etoposide	Toxicities according to CTCAE v5 will be summarized by frequencies and rates calculated as the proportion of patients in the safety population experiencing SAEs, discontinuations due to AEs, and AEs.	through study completion (i.e. up to 2 years)

Collaborators and Investigators

• Sponsor: Nabil Adra
• Investigators: Principal Investigator: Nabil Adra, MD, Indiana University

Publications and helpful links

General Publications

• Taza F, Abonour R, Zaid MA, Althouse SK, Anouti B, Akel R, Hanna NH, Adra N, Einhorn LH. Maintenance Oral Etoposide After High-Dose Chemotherapy (HDCT) for Patients With Relapsed Metastatic Germ-Cell Tumors (mGCT). Clin Genitourin Cancer. 2023 Apr;21(2):213-220. doi: 10.1016/j.clgc.2023.01.004. Epub 2023 Jan 18.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Germ Cell Tumor
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Nonseminomatous germ cell tumor; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Etoposide
• Other Study ID Numbers: CTO-IUSCCC-0742

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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