Radiation + Chemotherapy for Small Cell Lung Cancer

Recruiting at 933 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Carboplatin, Cisplatin, Etoposide

Disqualifiers: Pregnancy, Nursing, Prior radiotherapy, 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: Unknown

Duration: 12 weeks

731 Participants Needed

Trial Summary

What is the purpose of this trial?

Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that you should not have had prior radiotherapy or chemotherapy for small cell lung cancer, except for one cycle of specific chemotherapy drugs.

What data supports the effectiveness of the drug combination of carboplatin, cisplatin, and etoposide with radiation therapy for small cell lung cancer?

Research shows that the combination of cisplatin, carboplatin, and etoposide with radiation therapy has been effective in treating small cell lung cancer, with a high response rate in patients and a median survival time of 16.4 months in those who had not received prior treatment. ^{1 2 3 4 5}

Is the combination of radiation and chemotherapy safe for treating small cell lung cancer?

The combination of chemotherapy drugs like carboplatin, cisplatin, and etoposide with radiation therapy has been studied for small cell lung cancer and is generally considered safe, with common side effects including low blood cell counts, mild to moderate esophagitis (inflammation of the esophagus), and neutropenia (low white blood cell count). These treatments have shown moderate toxicity but are well tolerated by most patients. ^{3 5 6 7 8}

What makes the Radiation + Chemotherapy treatment for small cell lung cancer unique?

This treatment combines high-dose radiation with chemotherapy drugs like carboplatin, cisplatin, and etoposide, which are used together to target cancer cells more effectively. The use of high-dose radiation and the specific combination of these drugs aim to improve outcomes compared to standard treatments, although the balance of effectiveness and side effects is still being studied. ^{1 4 5 9 10}

Research Team

Jeffrey A. Bogart, MD

Principal Investigator

State University of New York - Upstate Medical University

Eligibility Criteria

This trial is for adults with limited-stage small cell lung cancer, who have measurable disease and haven't had complete surgical resection or prior chest radiotherapy. They can have received one cycle of specific chemotherapy. Key health metrics like blood counts and liver/kidney function must be within certain limits.

Inclusion Criteria

My cancer is confined to one side of my chest and has spread only to nearby lymph nodes.

I have had only one round of chemotherapy that included carboplatin or cisplatin and etoposide.

My lung cancer diagnosis was confirmed through lab tests.

Exclusion Criteria

I have not had surgery to completely remove my cancer.

I do not have fluid in my lungs or, if I do, it has been tested and is not cancerous.

I haven't had chemo or radiation for small cell lung cancer, except as noted before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive thoracic radiotherapy and chemotherapy. Radiotherapy is administered either as standard-dose (45 Gy over 3 weeks), higher-dose (70 Gy over 7 weeks), or mid-dose (61.2 Gy over 5 weeks). Chemotherapy with cisplatin or carboplatin and etoposide is given every 21 days for 4 cycles.

12 weeks

Prophylactic Cranial Irradiotherapy (PCI)

Within 3-6 weeks after completion of chemotherapy, PCI is offered to patients with a complete or near complete tumor response.

3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years or until disease progression.

10 years

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Etoposide
• High Radiation Dose Therapy
• Standard Radiation Dose Therapy

Trial Overview The study compares different doses of radiation therapy combined with chemotherapy drugs (cisplatin, etoposide, carboplatin) to see which regimen is more effective against limited-stage small cell lung cancer. It's a phase III trial where patients are randomly assigned to treatment groups.

Participant Groups

Group I: Arm B - High Dose Radiotherapy + Chemotherapy Experimental Treatment 4 Interventions

Radiotherapy (every day, Monday-Friday, for a total of 7 weeks) XRT: 70 Gy QD (2.0 Gy/fx), starting on day 1 of Cycle 1 or 2, every day, for 7 weeks Chemotherapy (every 21 days for 4 cycles, for a total of 12 weeks): * Cisplatin 80 mg/m2 IV on day 1 OR Carboplatin AUC 5 IV day 1, every 21 days * Etoposide 100 mg/m2 IV on days 1, 2, and 3, every 21 days

Group II: Arm A - Standard Radiotherapy + Chemotherapy Active Control 4 Interventions

Radiotherapy (every day, Monday-Friday, for a total of 3 weeks) XRT: 45 Gy BID (1.5 Gy/fx) starting on day 1 of Cycle 1 or 2, every day, for 3 weeks Chemotherapy (every 21 days for 4 cycles, for a total of 12 weeks): * Cisplatin 80 mg/m2 IV on day 1 OR Carboplatin AUC 5 IV day 1, every 21 days * Etoposide 100 mg/m2 IV Register/ on days 1, 2, and 3, every 21 days

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 90 patients with limited stage small cell lung cancer, concurrent radiotherapy combined with carboplatin and etoposide significantly improved median survival time to 26 months compared to 19 months for those receiving sequential treatment.

The 5-year survival rate was also better in the concurrent treatment group at 27%, versus 16% in the sequential group, indicating that concurrent treatment may be a more effective approach for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. Qiao, TK., Zhou, DA., Xin, L., et al.[2016]

In a study of 47 patients with limited disease small-cell lung carcinoma, the combination of carboplatin and etoposide followed by thoracic radiotherapy resulted in a 73% overall response rate, but the median survival time was only 13.7 months, indicating limited long-term efficacy.

The treatment was associated with significant adverse effects, including grade 3-4 neutropenia in 46% of patients and febrile neutropenia in 14%, highlighting safety concerns despite the initial response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. Yilmaz, U., Anar, C., Korkmaz, E., et al.[2022]

A combination treatment of paclitaxel, carboplatin, and oral etoposide was found to be highly effective and well tolerated in 117 patients with small-cell lung cancer, showing promising results in both extensive and limited stages of the disease.

The regimen can be safely administered alongside thoracic radiation therapy, with only a few patients experiencing esophagitis, indicating a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Hainsworth, JD., Hopkins, LG., Thomas, M., et al.[2015]

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]

In a pilot study of 40 patients with limited-stage small-cell lung carcinoma, concurrent chemotherapy with cisplatin and etoposide alongside radiotherapy resulted in a high complete response rate, with 23 patients showing complete remission.

The median survival for all patients was 18 months, and five patients survived over 2 years without therapy, indicating promising long-term outcomes and acceptable toxicity levels, primarily neutropenia and mild to moderate radiation-related effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study. McCracken, JD., Janaki, LM., Taylor, SB., et al.[2018]

The maximum tolerated dose (MTD) for the combination of etoposide and cisplatin with concurrent thoracic radiotherapy in Chinese patients with limited-stage small cell lung cancer was established as etoposide (100 mg/m2 on days 1-3) and cisplatin (75 mg/m2 on day 1).

The study, which included 20 patients, reported significant hematologic toxicities, with a 1-year overall survival rate of 91% and a progression-free survival rate of 61%, indicating that the treatment regimen is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation with Concurrent Twice-daily Radiotherapy for Patients with Limited-stage Small Cell Lung Cancer]. You, J., Yu, H., Song, M., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic Co-operative Oncology Group study. [2020]

2. 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]

3. Japan pubmed.ncbi.nlm.nih.gov

[Phase I/II study of a combination regimen composed of cisplatin, carboplatin and etoposide against small cell lung cancer]. [2013]

4. China pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. [2016]

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

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. [2022]

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

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. [2015]

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

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

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

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study. [2018]

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

A preliminary report: concurrent twice-daily radiotherapy plus platinum-etoposide chemotherapy for limited small cell lung cancer. [2019]

10. China pubmed.ncbi.nlm.nih.gov

[Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation with Concurrent Twice-daily Radiotherapy for Patients with Limited-stage Small Cell Lung Cancer]. [2018]