Oral Etoposide for Germ Cell Cancer

Overseen By Christin Snow, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nabil Adra

Must not be taking: Investigational agents

Disqualifiers: Active infection, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new use for the drug etoposide (also known as Eposin, VP-16, or Vepesid) to assist individuals with germ cell tumors (GCT) that have recurred after previous treatments. The trial aims to determine if regular oral administration of etoposide can improve outcomes compared to observation without additional treatment. Ideal participants have already undergone high-dose chemotherapy and a stem-cell transplant and currently show stable or decreasing tumor markers (substances in the blood that can indicate cancer). The study includes both active treatment and observation groups to compare results. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that etoposide is generally well-tolerated by patients with various types of cancer. It often treats cancers such as testicular, prostate, and lung cancer. In one study, etoposide was part of successful treatment plans for patients with germ-cell cancer.

However, like many treatments, etoposide can cause side effects. A study examining real-world data found that while some unexpected medical problems can occur, they are usually manageable. The most common side effects include low blood cell counts, which can increase the risk of infection, and mild nausea.

Overall, evidence suggests that etoposide is a safe option for many people, especially when used under careful medical supervision. Discussing potential risks with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for germ cell cancer?

Unlike the standard treatments for germ cell cancer, which often involve intravenous chemotherapy, oral etoposide offers a convenient oral administration. This delivery method can make treatment more accessible and less burdensome for patients who prefer taking medication at home instead of visiting a clinic for infusions. Researchers are excited about this option because it maintains the effectiveness of traditional etoposide while potentially improving quality of life and adherence to treatment.

What evidence suggests that oral etoposide could be an effective treatment for germ cell cancer?

Research has shown that oral etoposide may help treat relapsed germ cell tumors (GCT) after high-dose chemotherapy and stem-cell transplants. In this trial, participants in the "Maintenance Oral Etoposide" arm will receive daily oral etoposide. One study found that patients who took oral etoposide daily had a 55% chance of their cancer not worsening over two years, compared to 44% for those who did not take the drug. The overall survival rate was also better, with 61% of patients on etoposide living for at least two years, compared to 52% in the group that did not take it. Additionally, about 74% of patients on etoposide were free of the disease after around three years. These results suggest that oral etoposide can effectively manage relapsed GCT. ^{5 6 7 8 9}

Who Is on the Research Team?

Nabil Adra, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

Adults over 18 with relapsed non-seminomatous germ cell tumors (GCT) who've had high-dose chemotherapy and stem-cell transplant. They must have normal or improving tumor markers, good organ function, no active infections, and not be pregnant or breastfeeding. Participants need to agree to use effective contraception.

Inclusion Criteria

I am not able to have children due to age, surgery, or menopause.

My cancer is a type of non-seminoma based on tests.

My cancer returned after first treatment with a cisplatin combo.

Exclusion Criteria

Previous hypersensitivity to etoposide which did not recover with supportive care

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.

My seminoma cancer has come back after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance daily oral etoposide or are observed following high-dose chemotherapy and peripheral-blood stem-cell transplant

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Etoposide

Trial Overview

This phase II trial is testing if taking oral Etoposide after high-dose chemo helps patients with GCT more than just monitoring them without treatment. It's an open label study, meaning everyone knows which treatment they're getting.

How Is the Trial Designed?

Group I: Maintenance Oral Etoposide Experimental Treatment 1 Intervention

Maintenance daily oral Etoposide.

Group II: Observation Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Nabil Adra

Lead Sponsor

Trials

5

Recruited

190+

Published Research Related to This Trial

In a Phase II study involving 20 patients with hormone-refractory prostate carcinoma, the oral combination of cyclophosphamide and etoposide showed a 35% objective response rate, with one complete response and six partial responses based on PSA levels.

The treatment was well tolerated, with minimal toxicities, and resulted in improved performance status for 26% of patients and relief of bone pain in 71%, indicating its potential efficacy in managing symptoms and disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the oral cyclophosphamide and oral etoposide combination in hormone-refractory prostate carcinoma patients. Maulard-Durdux, C., Dufour, B., Hennequin, C., et al.[2019]

In a phase II trial involving 22 patients with recurrent ovarian carcinoma, oral etoposide (VP-16-213) showed some antitumor activity, with one patient achieving a complete response and another a partial response.

The treatment was associated with significant toxicity, as 14 patients experienced grade 3-4 hematologic toxicity, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of VP-16-213 (etoposide) administered orally in advanced ovarian cancer. Hansen, F., Malthe, I., Krog, H.[2019]

The absolute oral bioavailability of etoposide in cancer patients ranges from 48% to 57%, indicating that nearly half of the orally administered dose is effectively absorbed into the bloodstream.

Significant variability in pharmacokinetics was observed among patients, suggesting that individual factors greatly influence how etoposide is processed, highlighting the need for personalized dosing strategies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and pharmacokinetics of etoposide (VP-16). Smyth, RD., Pfeffer, M., Scalzo, A., et al.[2013]

In a study of 34 heavily pretreated germ cell cancer patients, maintenance daily oral etoposide (VP-16) was well tolerated, with the most significant side effect being leukopenia, affecting a few patients severely.

Among patients who started VP-16 in complete remission, 74% remained disease-free after a median follow-up of 36 months, suggesting that this treatment may be effective in maintaining remission in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors. Cooper, MA., Einhorn, LH.[2017]

In a study of 178 patients with disseminated germ cell tumors, the addition of bleomycin to the chemotherapy regimen (PVP16B) significantly improved treatment outcomes compared to a regimen without bleomycin (PVP16), with a failure-free survival rate of 86% versus 69%.

Patients receiving the PVP16B regimen also had a higher overall survival rate of 95% compared to 86% in the PVP16 group, highlighting the importance of bleomycin in achieving better therapeutic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. Loehrer, PJ., Johnson, D., Elson, P., et al.[2017]

In a study of 31 women with platinum-resistant epithelial ovarian cancer, etoposide (VP16) showed a response rate of 26%, indicating some effectiveness in this challenging condition.

The treatment was given as a fixed dose of 100 mg daily for 14 days every 3 weeks, but the response durations were short, suggesting that while VP16 has activity, its long-term efficacy may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide is active against platinum-resistant epithelial ovarian cancer. Hoskins, PJ., Swenerton, KD.[2017]

In a phase II study involving 22 women with advanced ovarian cancer resistant to platinum-based chemotherapy, oral VP16 (etoposide) demonstrated an objective response rate of 18%, with one complete response and three partial responses, indicating its potential efficacy as a second-line treatment.

The treatment was generally well-tolerated, with mild toxicity reported; however, some patients experienced severe myelotoxicities, including grade III/IV thrombocytopenia and neutropenia, but there were no treatment-related deaths, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide (VP16) in platinum-resistant epithelial ovarian cancer (EOC). Alici, S., Saip, P., Eralp, Y., et al.[2013]

In a phase II study involving 83 evaluable patients with genitourinary tumors, Etoposide (VP-16) showed limited efficacy, with only 6.3% of testicular cancer patients and 7.7% of prostatic cancer patients responding to treatment, while no responses were observed in bladder and renal cancer patients.

The treatment was associated with significant side effects, including alopecia, gastrointestinal issues, and myelosuppression, with leukopenia affecting 66.3% of patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of etoposide (VP-16-213) in genitourinary tumors. VP-16-213 Genitourinary Study Group]. Suzuki, K.[2013]

In a study of 21 children with progressive or recurrent sarcomas, oral etoposide (VP-16) showed a modest efficacy with a 14% objective response rate, including one complete response and two partial responses after two treatment courses.

Oral VP-16 was found to be relatively nontoxic, with no major acute toxicities reported, making it a simple treatment option for children, although the cure rate is low and it may be more suitable for palliative care in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide for recurrent/progressive sarcomas of childhood. Kebudi, R., Görgün, O., Ayan, I.[2013]

Chronic oral VP-16 (Etoposide) was administered to 8 patients with locally recurrent medulloblastoma, showing that it is a well-tolerated chemotherapy option with manageable side effects, including partial alopecia and neutropenia.

Out of the 8 patients, 62.5% experienced either stable disease or partial responses lasting between 4 to 10 months, indicating that VP-16 has potential efficacy in treating this type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic oral VP-16 for recurrent medulloblastoma. Chamberlain, MC., Kormanik, PA.[2019]

In a Phase I trial involving 18 patients with advanced cancer, the maximum tolerated dose of etoposide (VP-16) given as a continuous intravenous infusion was determined to be 150 mg/m2/day for patients in good health, with hematological toxicity being the main side effect observed.

The study found that patient age significantly influenced the plasma clearance of VP-16, and the recommended dose for further Phase II trials is 150 mg/m2/day, as this dosage showed manageable side effects like mild nausea and hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacological study of 72-hour continuous infusion of etoposide in patients with advanced cancer. Bennett, CL., Sinkule, JA., Schilsky, RL., et al.[2013]

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Etoposide is a medication used in the management and treatment of various cancers such as testicular, prostate, bladder, stomach, and lung cancer.

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ETOPOSIDE 1. Exposure Data

(1993) reviewed the records of 538 previously untreated patients with (disseminated) germ-cell cancer entering clinical trials between 1982 and 1991,. ETOPOSIDE.