Chemotherapy for Cancer

Recruiting at 600 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Prior systemic therapy, Radiation therapy, Respiratory disease, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 23

Duration: 9-12 weeks

1780 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether carboplatin or cisplatin is the best chemotherapy drug for treating metastatic germ cell tumors, which are cancerous and have spread beyond their original location. The trial also examines how well active surveillance (also known as watchful waiting or observation) helps doctors monitor for tumor recurrence after removal. Participants may qualify if they have been newly diagnosed with a stage I germ cell tumor and have not previously received systemic therapy or radiation for this cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 this with the trial coordinators or your doctor to get a clear answer.

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

Research shows that the chemotherapy treatments under study, which include combinations of bleomycin, etoposide, carboplatin, and cisplatin, have specific safety profiles.

For treatments with bleomycin, etoposide, and carboplatin, studies have identified some risks. Bleomycin can cause lung problems, and etoposide may lead to blood issues, including a small risk of leukemia. In young patients, these drugs have been tested to understand their side effects, which can include potential lung and heart problems.

For treatments with bleomycin, etoposide, and cisplatin, long-term studies have shown a high survival rate of about 87% over five years, but risks remain. Similar to the carboplatin combination, there is a small chance of developing leukemia. Additionally, cisplatin can cause tissue damage if it leaks from the vein.

These treatments have been studied extensively, providing a good understanding of their safety. While risks exist, the treatments are also known to be effective for certain cancers. Participants should consider these factors when thinking about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore several chemotherapy combinations that could offer new hope for patients with certain types of testicular and ovarian germ cell tumors. Unlike traditional chemotherapy regimens, these treatments combine drugs like bleomycin, etoposide, carboplatin, and cisplatin in various ways to potentially improve effectiveness and manage toxicity. The trial's observation arm for low-risk patients is distinctive; it focuses on active surveillance instead of immediate treatment, which could minimize unnecessary exposure to chemotherapy. This approach could lead to more personalized treatment plans, reducing side effects while ensuring effective cancer control.

What evidence suggests that this trial's treatments could be effective for metastatic germ cell tumors?

Research has shown that both bleomycin-etoposide-carboplatin and bleomycin-etoposide-cisplatin effectively treat germ cell tumors. In this trial, participants may receive either the bleomycin-etoposide-carboplatin combination or the bleomycin-etoposide-cisplatin combination. Specifically, a study found that 98.5% of patients treated with bleomycin-etoposide-carboplatin survived for at least two years, indicating positive outcomes. In contrast, bleomycin-etoposide-cisplatin achieved a complete response rate of 94.4%, with nearly all tumors disappearing after treatment. These treatments kill cancer cells and prevent their growth, making both combinations promising options for treating germ cell tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

A. L Frazier

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for pediatric and adult patients with various types of germ cell tumors, including those in the ovaries or testes. It's open to all ages for certain low-risk conditions but has specific age criteria for standard risk groups. Participants must have adequate organ function and no prior treatments for their current cancer diagnosis.

Inclusion Criteria

I am between 11 and 25 years old.

I am healthy enough to undergo the treatment outlined in the study without any medical reasons preventing me.

I have a low-risk, early-stage testicular cancer without certain aggressive features.

Exclusion Criteria

I haven't had radiation therapy, except possibly for brain metastases if I'm under 11.

I have not received any systemic therapy for my current cancer.

I do not have severe lung problems that prevent me from taking bleomycin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Patients with low-risk stage I germ cell tumors undergo observation for recurrence after tumor removal

Up to 2 years

Regular imaging and blood sample collection

Treatment

Patients with standard risk germ cell tumors receive chemotherapy with either carboplatin or cisplatin-based regimens

9-12 weeks

Every 21 days for up to 3-4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 2 months for 12 months, every 3-6 months to 24 months, every 6 months for years 3-5, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Active Surveillance
• Bleomycin
• Carboplatin
• Cisplatin
• Etoposide

Trial Overview The study monitors low-risk germ cell tumor recurrence post-surgery and compares chemotherapy drugs (bleomycin, carboplatin, etoposide, cisplatin) in treating metastatic standard risk tumors. It includes imaging tests like MRI and CT scans, pulmonary tests, quality-of-life assessments, biopsies, and genetic studies.

How Is the Trial Designed?

Group I: Low-Risk (observation) Experimental Treatment 8 Interventions

Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I non-seminoma or seminoma MGCTs undergo observation and can transfer to standard risk arm when eligibility criteria are met. Patients with stage I seminoma testicular MGCT undergo observation, and those with residual/recurrent disease are treated at the discretion of their physician. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial.

Group II: Arm IV (bleomycin, etoposide, cisplatin) Experimental Treatment 11 Interventions

Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.

Group III: Arm III (bleomycin, etoposide, carboplatin) Experimental Treatment 11 Interventions

Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.

Group IV: Arm II (bleomycin, etoposide, cisplatin) Experimental Treatment 11 Interventions

Patients receive bleomycin IV over 10 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.

Group V: Arm I (bleomycin, carboplatin, etoposide) Experimental Treatment 11 Interventions

Patients receive bleomycin IV over 10 minutes and carboplatin IV over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.

Active Surveillance is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Approved in European Union as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Approved in Canada as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Approved in Japan as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cisplatin-based regimens, particularly when combined with drugs like etoposide, vindesine, and mitomycin-C, have shown a reproducible response rate of 30% to 40% in patients with non-small-cell lung cancer.

Patients with good performance status should be encouraged to participate in clinical trials, as current therapies need improvement and may offer better options than standard chemotherapy, especially for those who are nonresponders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of non-small-cell lung cancer. Klastersky, J., Sculier, JP.[2018]

In a pilot phase II trial involving 31 high-risk patients with advanced non-small cell lung cancer (NSCLC), a novel metronomic regimen of weekly cisplatin and oral etoposide showed a promising objective response rate of 45.2%, indicating significant anti-tumor activity.

The treatment was generally well tolerated, although some patients experienced severe side effects like leukopenia and anemia, and three patients died from pulmonary embolism; however, the regimen demonstrated a mean survival time of 13 months, suggesting potential benefits even for patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients. Correale, P., Cerretani, D., Remondo, C., et al.[2022]

In a study involving 14 advanced breast cancer patients who had already undergone extensive chemotherapy, the combination of cisplatin and etoposide showed minimal effectiveness, with only one patient experiencing a minor response and the majority either showing no change or disease progression.

The treatment was poorly tolerated, with severe nausea and vomiting reported in 62% of patients and significant leukopenia in 31%, leading to two patients refusing further treatment due to the side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and etoposide in chemotherapy-refractory advanced breast cancer. Giaccone, G., Donadio, M., Ferrati, P., et al.[2022]

Cisplatin plus VP-16 has shown high response rates (71% to 94%) and complete remission rates (30% to 53%) in treating patients who have failed previous CAV chemotherapy, based on data from four studies involving 238 patients.

Current studies, including a Southeastern Cancer Study Group protocol, indicate that using cisplatin plus VP-16 as part of the initial treatment strategy may provide a significant survival advantage compared to traditional CAV alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial therapy with cisplatin plus VP-16 in small-cell lung cancer. Einhorn, LH.[2018]

In a study of 156 patients with advanced non-small-cell lung cancer (NSCLC), combination chemotherapy with cisplatin and etoposide resulted in a 30% response rate, significantly improving median survival to 35 weeks compared to 18 weeks with cisplatin alone.

The addition of mitomycin C to the cisplatin and etoposide regimen did not enhance the therapeutic response, and the main side effect observed was myelosuppression, particularly in the mitomycin C group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial fo three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group. Crino, L., Tonato, M., Darwish, S., et al.[2019]

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

A systematic review of 36 clinical trials found that chemotherapy regimens including cisplatin (CDDP) and/or etoposide (VP16) significantly improve survival rates in patients with small cell lung cancer (SCLC), with combined hazard ratios indicating a clear survival benefit for both drugs.

Specifically, regimens containing etoposide alone or in combination with cisplatin showed strong evidence of effectiveness, with hazard ratios of 0.72 for VP16 and 0.57 for combinations, suggesting these treatments should be prioritized in SCLC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. Mascaux, C., Paesmans, M., Berghmans, T., et al.[2019]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Paclitaxel has been established as an effective treatment for newly diagnosed ovarian cancer patients, leading to its incorporation into primary chemotherapy regimens, particularly in combination with cisplatin as the new standard in the U.S.

Ongoing clinical trials are exploring various strategies to optimize paclitaxel-based chemotherapy, including comparisons of different platinum-based drugs and infusion schedules, as well as evaluating high-dose therapies with stem cell support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. Ozols, RF., Vermorken, JB.[2015]

In a trial involving 228 patients with advanced non-small-cell lung cancer, cisplatin (CDDP) combined with etoposide showed a higher objective response rate (27%) compared to carboplatin (CBDCA) with etoposide (16%), although this difference was not statistically significant (P = .07).

Cisplatin treatment was associated with significantly increased toxicity, particularly myelosuppression and renal function impairment, indicating that while it may be more effective, it also poses greater risks compared to carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. Klastersky, J., Sculier, JP., Lacroix, H., et al.[2017]

The combination of orally administered VP-16 (etoposide) and JM-216 (a platinum analog) showed therapeutic synergy in mice with leukemia, allowing for significantly lower doses of each drug compared to their maximum tolerated doses when used alone.

While the combination was effective in the leukemia model, it did not demonstrate the same synergy in a sarcoma model, suggesting that the effectiveness of this drug combination may vary depending on the type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy involving orally administered etoposide and JM-216 in murine tumor models. Rose, WC.[2014]

Cisplatin (CDDP) has been a key treatment for various cancers since 1972, but its use is limited by significant toxicities, particularly renal impairment.

Carboplatin (CBDCA), a second-generation analogue of cisplatin, has shown reduced renal toxicity and is effective against advanced cancers, although it can cause myelosuppression, particularly affecting platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. Ariyoshi, Y., Ota, K.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/1702147/

Effectiveness of carboplatin, etoposide, and bleomycin ... The 2-year cause-specific survival probability was 98.5%, the single cause-related mortality being caused by bleomycin pneumonitis. Five patients failed CEB ...

2. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.1991.9.1.62

Effectiveness of Carboplatin, Etoposide, and Bleomycin ... Using the Indiana University classifi- cation, 68 patients had minimal disease, six had moderate disease (three with more than five lung metastases per field,.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9164194/

Randomized trial of bleomycin, etoposide, and cisplatin ... Results: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804919308962

Long-term outcomes with intensive induction ... Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy.

5. ejcancer.com ejcancer.com/article/0277-5379(91)90167-C/fulltext

Carboplatin dose in combination chemotherapy for ... Carboplatin was given in escalating doses in combination with etoposide and bleomycin (CEB) to 36 patients with testicular cancer.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK304323/

ETOPOSIDE IN COMBINATION WITH CISPLATIN AND ... - NCBI Etoposide in combination with cisplatin and bleomycin causes acute myeloid leukaemia. There is limited evidence in humans for the carcinogenicity of etoposide ...

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Etoposide, Carboplatin, and Bleomycin in Treating Young ... Determine the toxic effects of etoposide, carboplatin, and bleomycin in young patients with malignant germ cell tumors. OUTLINE: Patients are ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143910003273

An alternative treatment regimen of advanced seminoma ... In addition, bleomycin treatment can result in pulmonary toxicity. Furthermore, direct vascular changes as well as an increased risk of late cardiovascular ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.1997.15.5.1844

Randomized trial of bleomycin, etoposide, and cisplatin ... This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

10. ejcancer.com ejcancer.com/article/S0959-8049(19)30896-2/fulltext

A randomised phase II trial (ISRCTN53643604) Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) ...