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

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the drug etoposide for treating germ cell cancer?

Research shows that oral etoposide has been effective in treating platinum-resistant ovarian cancer, with some patients experiencing tumor shrinkage or stable disease. This suggests it may also be beneficial for germ cell cancer, especially after other treatments. ^{1 2 3 4 5}

Is oral etoposide safe for humans?

Oral etoposide has been studied in various cancers and is generally considered safe, but it can cause side effects like hair loss, nausea, vomiting, and blood-related issues such as low white blood cell counts. Most side effects are mild, but some patients may experience severe blood-related toxicities. ^{1 3 6 7 8}

How is oral etoposide different from other drugs for germ cell cancer?

Oral etoposide is unique because it is administered in pill form, making it more convenient than intravenous treatments. It is used as maintenance therapy after initial treatment, which is not common for all germ cell cancer drugs. ^{2 3 9 10 11}

Research Team

Nabil Adra, MD

Principal Investigator

Indiana University

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bioavailability and pharmacokinetics of etoposide (VP-16). [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Oral etoposide (VP16) in platinum-resistant epithelial ovarian cancer (EOC). [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Oral etoposide is active against platinum-resistant epithelial ovarian cancer. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of VP-16-213 (etoposide) administered orally in advanced ovarian cancer. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacological study of 72-hour continuous infusion of etoposide in patients with advanced cancer. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Oral etoposide for recurrent/progressive sarcomas of childhood. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Phase II study of the oral cyclophosphamide and oral etoposide combination in hormone-refractory prostate carcinoma patients. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Chronic oral VP-16 for recurrent medulloblastoma. [2019]