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

NCT04804007 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0742
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

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

Keywords

Germ Cell Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

  through study completion (i.e. up to 2 years)

Study Arms (2)

Maintenance Oral Etoposide

EXPERIMENTAL

Maintenance daily oral Etoposide.

Drug: Etoposide

Observation

NO INTERVENTION

If randomized to Observation, subjects will jump to follow-up.

Interventions

Etoposide DRUG

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.

Maintenance Oral Etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information
• Age ≥ 18 years at the time of consent
• Histological or serological evidence of non-seminomatous GCT
• Relapsed disease after first-line cisplatin-based combination chemotherapy
• Completed salvage treatment with HDCT and PBSCT for 2 tandem cycles per Institutional Guidelines
• 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 \[cisplatin+vinblastine+bleomycin\]
• Normal or declining tumor markers (AFP and hCG) at time of screening
• Adverse events from prior therapy recovered to CTCAE v5.0 grade ≤ 2 at time of registration
• Women with ovarian germ cell tumors are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 28 days of study registration
• Last dose of HDCT must be ≤16 weeks from study registration
• 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
• 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
• If a female of childbearing potential, a negative urine pregnancy test within 28 days prior to receiving the first dose of study drug.

You may not qualify if:

• Relapsed pure seminoma
• Rising tumor markers (AFP and hCG) at time of screening
• Patients who completed 2nd cycle of HDCT (time since last dose of HDCT) \>16 weeks ago
• Treatment with any investigational agent within 28 days prior to study registration
• Other active malignancy requiring treatment in past 12 months
• History of psychiatric illness or social situations that would limit compliance with study requirements
• Active infection requiring systemic therapy
• Previous hypersensitivity to etoposide which did not recover with supportive care
• Pregnancy, lactation, or breastfeeding
• 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.

Sponsors & Collaborators

• Nabil Adra: lead

Study Sites (1)

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 36737276 DERIVED

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Nonseminomatous germ cell tumor

Interventions

Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Nabil Adra, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christin Snow, RN

CONTACT

317-274-5830; chsnow@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Patients who completed HDCT+PBSCT within the past 16 weeks will enroll and randomize in 1:1 fashion in blocks of 8 to maintenance daily oral etoposide 50mg vs. observation only. Randomization will be stratified based on: -Presence of platinum refractory disease status defined by radiographic or serologic progression within 4 weeks of first-line cisplatin-based combination chemotherapy: yes vs. no

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 18, 2021
• Study Start: March 3, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)