Chemotherapy for Cancer

Recruiting at574 trial locations

Overseen by A. L Frazier

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Children's Oncology Group

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well active surveillance help doctors to monitor subjects with low risk germ cell tumors for recurrence after their tumor is removed. When the germ cell tumor has spread outside of the organ in which it developed, it is considered metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The trial studies whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic standard risk germ cell tumors.

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.

What data supports the effectiveness of the drugs used in the chemotherapy for cancer trial?

Research shows that combinations of cisplatin and etoposide have been effective in treating non-small-cell lung cancer, with response rates ranging from 26% to 38% in various studies. These drugs have shown activity in cancer treatment, although they can also cause significant side effects. ^{1 2 3 4 5}

What safety data exists for chemotherapy drugs like cisplatin, carboplatin, and etoposide?

Cisplatin can cause side effects like nausea, kidney problems, nerve damage, hearing loss, and low blood cell counts. Carboplatin is less harmful to the kidneys but can lead to more blood-related issues, such as low platelet counts. Etoposide may cause nausea, vomiting, and low white blood cell counts. These drugs have been studied in various cancers, showing different levels of safety and side effects. ^{3 5 6 7 8}

How does the chemotherapy drug combination of Bleomycin, Carboplatin, Cisplatin, and Etoposide differ from other cancer treatments?

This chemotherapy drug combination is unique because it includes a mix of drugs like Bleomycin, Carboplatin, Cisplatin, and Etoposide, which are known for their effectiveness in treating various cancers, such as small cell lung cancer and ovarian cancer, by targeting cancer cells in different ways. The combination aims to enhance treatment efficacy by using multiple drugs that work together, potentially offering a broader attack on cancer cells compared to single-drug therapies. ^{8 9 10 11 12}

Research Team

A. L Frazier

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Active Surveillance (Procedure)
• Bleomycin (Anti-tumor antibiotic)
• Carboplatin (Alkylating agents)
• Cisplatin (Alkylating agents)
• Etoposide (Topoisomerase II inhibitors)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Doug Hawkins

Children's Oncology Group

Chief Executive Officer since 2020

MD from University of Washington School of Medicine

Dr. Leo Mascarenhas

Children's Oncology Group

Chief Medical Officer since 2024

MD, MS from Cedars-Sinai Guerin Children’s

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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 (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]

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]

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]

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]

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]

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]

References

1. Germany 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. [2019]

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

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

3. United States 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. [2017]

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

Chemotherapy of non-small-cell lung cancer. [2018]

5. Greece 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. [2022]

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

Cisplatin and etoposide in chemotherapy-refractory advanced breast cancer. [2022]

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

[Second-generation cisplatin analogs]. [2013]

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

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

Treatment of ovarian cancer: current status. [2015]

10. Ireland 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. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

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

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

Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]