Chemotherapy + Radiation + Bevacizumab for Lung Cancer

Recruiting at 69 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants

Disqualifiers: Brain metastases, Uncontrolled hypertension, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 23

29 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take full-dose anticoagulants or other anticancer therapies during the trial.

What data supports the effectiveness of the drug Bevacizumab in treating lung cancer?

Research shows that adding Bevacizumab to standard chemotherapy for advanced non-small cell lung cancer (NSCLC) significantly increased the time before the cancer progressed and improved response rates compared to chemotherapy alone. In patients with certain types of NSCLC, survival times were also longer with Bevacizumab. ^{1 2 3 4 5}

Is the combination of chemotherapy, radiation, and Bevacizumab safe for lung cancer treatment?

Bevacizumab, when used with chemotherapy for lung cancer, has been associated with risks like high blood pressure and protein in urine, but these are usually manageable. However, there is a risk of serious side effects like bleeding in the lungs and bowel perforation, especially in certain patients, so careful selection of patients is important to minimize these risks. ^{4 6 7 8 9}

What makes the treatment of Chemotherapy + Radiation + Bevacizumab for Lung Cancer unique?

This treatment combines chemotherapy, radiation, and bevacizumab (a drug that inhibits blood vessel growth in tumors) to potentially improve survival in lung cancer patients. Bevacizumab, when used with platinum-based chemotherapy, has shown to prolong survival in advanced non-small-cell lung cancer, making this combination a promising approach compared to traditional treatments. ^{3 8 10 11 12}

What is the purpose of this trial?

This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin, etoposide, and docetaxel, work in different ways to stop the growth of \[cancer/tumor\] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with radiation therapy and bevacizumab may kill more tumor cells.

Research Team

Antoinette J Wozniak

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with newly diagnosed stage III non-small cell lung cancer that can't be removed by surgery. They should not have had previous treatments for lung cancer, no serious wounds or fractures, and must not be pregnant or nursing. Participants need to meet specific medical criteria like normal kidney function and blood counts, and they cannot have brain metastases or other conditions that pose a high risk of bleeding.

Inclusion Criteria

Meets 1 of the following risk criteria:

Your disease can be seen on a CT scan or MRI.

My condition cannot be treated with surgery.

Exclusion Criteria

I do not have a serious heart rhythm problem that needs medication.

You need to have a negative pregnancy test.

I have no cancer history except for certain skin cancers, early-stage cancers in remission, or any cancer I've been free from for 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive cisplatin, etoposide, and thoracic radiotherapy, with or without bevacizumab, over a period of several weeks

7 weeks

Daily visits for radiotherapy, additional visits for chemotherapy administration

Consolidation Chemotherapy

Patients receive docetaxel and bevacizumab, with supportive care using filgrastim or pegfilgrastim

9 weeks

Every 21 days for 3 courses

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Every 2-3 months for 2 years, then every 6 months

Treatment Details

Interventions

• Bevacizumab
• Cisplatin
• Docetaxel
• Etoposide
• Radiation Therapy

Trial Overview The study tests a combination of chemotherapy drugs (cisplatin, etoposide, docetaxel), radiation therapy, and the monoclonal antibody bevacizumab. The goal is to see if this mix can better kill tumor cells by stopping their growth and cutting off their blood supply compared to standard treatments.

Participant Groups

Group I: Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab) Experimental Treatment 7 Interventions

Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.

Group II: Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab) Experimental Treatment 7 Interventions

Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.

Group III: Group 1 (cisplatin, etoposide, radiotherapy) Experimental Treatment 6 Interventions

Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

Combined chemotherapy and radiation therapy is more effective than radiation therapy alone for treating unresectable non-small cell lung cancer, although the best timing for chemotherapy (concurrent vs. sequential) is still uncertain.

In patients with stage IIIa and IIIb disease, surgery after neoadjuvant chemotherapy and radiation therapy shows comparable resectability and survival rates, but the impact of surgery on overall survival remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current management of unresectable non-small cell lung cancer. Livingston, RB.[2018]

In a study of 17 previously treated patients with non-small cell lung carcinoma (NSCLC), the combination therapy of carboplatin-paclitaxel plus bevacizumab (TC+Bev) showed an objective response rate of 17.6% and a disease control rate of 70.6%, indicating its potential efficacy as a second-line treatment.

The treatment was well-tolerated with no treatment-related deaths reported, and the median progression-free survival was 4.7 months, suggesting that TC+Bev has an acceptable safety profile for patients with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of chemotherapy with carboplatin-paclitaxel plus bevacizumab for previously treated patients with advanced non-small cell carcinoma]. Maki, S., Igawa, S., Otani, S., et al.[2015]

Cisplatin combined with other agents like vinblastine or etoposide shows promise as an effective pre-radiotherapy treatment for locally advanced non-small cell lung cancer (NSCLC), but optimal scheduling is still being researched.

In a study of 170 patients, concurrent chemotherapy with carboplatin and radiation led to increased toxicity, including significantly higher rates of neutropenia and thrombocytopenia, indicating that while this approach may improve treatment efficacy, it also raises safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. Bishop, JF.[2019]

In a study of 25 patients with stage IIIa lung adenocarcinoma, the combination of bevacizumab with pemetrexed and carboplatin as neoadjuvant chemotherapy showed a safety profile with manageable adverse events, including some cases of fatigue, neutropenia, and hypertension.

No severe perioperative complications such as hemorrhage or thromboembolic events were observed, suggesting that the neoadjuvant treatment is well-tolerated and safe for patients undergoing surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin in Patients with IIIa Lung Adenocarcinoma]. Zhang, S., Xu, P., Yuan, C., et al.[2019]

Bevacizumab (Avastin®) is the only antiangiogenic agent approved for first-line treatment of advanced non-small-cell lung cancer (NSCLC) in eligible patients, effectively targeting the VEGF signaling pathway to inhibit tumor growth and metastasis.

While there are concerns about severe side effects like pulmonary hemorrhage, recent studies suggest that bevacizumab is safe and well-tolerated even in patients typically excluded from clinical trials, indicating potential for broader use in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in the treatment of NSCLC: patient selection and perspectives. Russo, AE., Priolo, D., Antonelli, G., et al.[2023]

Bevacizumab, an angiogenesis inhibitor, has been shown to significantly prolong overall survival and progression-free survival in patients with inoperable, advanced non-small-cell lung cancer when used with chemotherapy, based on two recent phase-III studies.

While bevacizumab can cause manageable side effects like hypertension and proteinuria, careful patient selection can minimize the risk of serious complications such as pulmonary bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bevacizumab in the first-line therapy of advanced NSCLC]. Hasenöhrl, N.[2018]

Bevacizumab, a drug used in combination with chemotherapy for non-small cell lung cancer, can lead to serious gastrointestinal complications, such as colonic perforation, even in patients without known risk factors.

A case study of a 69-year-old patient revealed that after two cycles of chemotherapy including bevacizumab, the patient developed ischemic colitis, highlighting the need for vigilance in monitoring for abdominal pain in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bowel perforation in non-small cell lung cancer after bevacizumab therapy. Schellhaas, E., Loddenkemper, C., Schmittel, A., et al.[2021]

In a study involving 987 patients with advanced non-small-cell lung cancer (NSCLC), bevacizumab combined with platinum-based chemotherapy showed a median progression-free survival of 7.4 months and an overall response rate of 45.6%, confirming its effectiveness as a first-line treatment.

The safety profile of bevacizumab was consistent with previous studies, with 33.6% of patients experiencing grade ≥3 adverse drug reactions, primarily leukopenia, neutropenia, and hypertension, but no new safety concerns were identified, indicating it is well tolerated even after more than 20 treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AVAiLABLE NIS - AVASTIN® in lung cancer treatment in routine oncology practice in Germany. Zahn, MO., Linck, D., Losem, C., et al.[2020]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

References

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

Non-small cell lung cancer and antiangiogenic therapy: what can be expected of bevacizumab? [2019]

2. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

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

Current management of unresectable non-small cell lung cancer. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy of chemotherapy with carboplatin-paclitaxel plus bevacizumab for previously treated patients with advanced non-small cell carcinoma]. [2015]

5. Ireland pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. [2019]

6. China pubmed.ncbi.nlm.nih.gov

[Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin in Patients with IIIa Lung Adenocarcinoma]. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab in the treatment of NSCLC: patient selection and perspectives. [2023]

8. Austria pubmed.ncbi.nlm.nih.gov

[Bevacizumab in the first-line therapy of advanced NSCLC]. [2018]

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

Bowel perforation in non-small cell lung cancer after bevacizumab therapy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Combination therapy involving radiofrequency ablation and targeted chemotherapy with bevacizumab plus paclitaxel and cisplatin in a rabbit VX2 lung tumor model. [2018]

11. England pubmed.ncbi.nlm.nih.gov

AVAiLABLE NIS - AVASTIN® in lung cancer treatment in routine oncology practice in Germany. [2020]

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

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]