Chemotherapy + Radiation + Bevacizumab for Lung Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs, radiation therapy, and bevacizumab (also known as Avastin, an anti-cancer medication) to treat stage III non-small cell lung cancer that surgery cannot remove. The goal is to determine if this combination can more effectively stop cancer growth and spread by directly attacking tumor cells and cutting off their blood supply. People newly diagnosed with this type of lung cancer who cannot undergo surgery might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research has shown that combining cisplatin, etoposide, and bevacizumab with radiation therapy has been tested for safety in people. Results indicate that this treatment is generally well-tolerated, though some side effects occur. In one study, participants experienced serious side effects such as low blood counts and fatigue, common with chemotherapy and radiation. Bevacizumab, which helps block the blood supply to tumors, was also part of this treatment. Previous research found that adding bevacizumab to chemotherapy improved outcomes compared to past data, but it also caused additional side effects like high blood pressure and bleeding. These side effects can vary in severity for each person. Overall, while the treatment can be effective, it can also cause significant side effects that require monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy, radiation, and Bevacizumab for lung cancer because Bevacizumab, a monoclonal antibody, targets and inhibits VEGF (vascular endothelial growth factor), which is crucial for tumor blood vessel formation. Unlike the standard treatments such as just chemotherapy or radiation alone, the addition of Bevacizumab offers a novel mechanism by potentially disrupting the tumor's blood supply, which may enhance the effectiveness of existing therapies. Additionally, the study explores different timing schedules for Bevacizumab administration, which could optimize its efficacy in combination with traditional therapies like Cisplatin and Etoposide.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will evaluate the combination of chemotherapy, radiation, and bevacizumab for treating lung cancer. Participants in different arms of the trial will receive varying combinations of these treatments. Bevacizumab, a medicine that blocks blood flow to tumors, may slow their growth. When combined with the chemotherapy drugs cisplatin and etoposide, this approach has shown promise in slowing tumor growth. Radiation therapy, which uses high-energy rays to kill cancer cells, has also been shown to help people with advanced lung cancer live longer. Together, these treatments might offer a more effective way to fight stage III non-small cell lung cancer that cannot be removed by surgery. ^{1 2 3 6 7}

Who Is on the Research Team?

Antoinette J Wozniak

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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

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

Meets 1 of the following risk criteria:

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4497941/

A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by ... VEGFR inhibitors have been evaluated in preclinical lung cancer models and have shown tumor growth delay when given with radiation especially on a concurrent ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00387699

Bevacizumab, Cisplatin, Etoposide, and Radiation Therapy ... Histologically or cytologically confirmed small cell lung cancer (SCLC) · Measurable disease · No malignant pleural effusion, contralateral hilar ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5652673/

PMC - PubMed Central Radiotherapy prolongs the survival of advanced non-small-cell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00334815?tab=table

NCT00334815 | Combination Chemotherapy, Radiation ... This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in treating patients with newly diagnosed stage III non-small cell ...

5. patlynk.com patlynk.com/trial/NCT00387699

Bevacizumab, Cisplatin, Etoposide, and Radiation Therapy ... PURPOSE: This phase II trial is studying how well giving bevacizumab together with cisplatin, etoposide, and radiation therapy works in treating patients with ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2009.23.7545

Phase II Study of Cisplatin Plus Etoposide and ... The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730415001370

Cisplatin, Etoposide, and Bevacizumab Regimen Followed ... Median progression-free survival was 7.8 months (95% CI, 7.0-11.3 months) and median overall survival was 13.2 months (95% CI, 11.8-18.7 months). Grade 3 to 4 ...