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

Nabil Adra

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Etoposide

Study type: Interventional

Funder types: Other

Identifiers

NCT04804007

CTO-IUSCCC-0742

Details and patient eligibility

About

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).

Full 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.

Enrollment: 64 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 with partners of childbearing potential, 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

64 participants in 2 patient groups

Maintenance Oral Etoposide

Experimental group

Description:

Maintenance daily oral Etoposide.

Treatment:

Drug: Etoposide

Observation

No Intervention group

Description:

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