Brigatinib + Bevacizumab for Lung Cancer

Recruiting at 6 trial locations

Overseen By Victoria Villaflor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Northwestern University

Must be taking: ALK-directed therapy

Must not be taking: Monoclonal antibodies, TKIs, others

Disqualifiers: Pregnancy, Cardiovascular disease, Infections, others

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

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

Compensation: Varies

Number of Visits: 31

Duration: Up to 3 years

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests brigatinib and bevacizumab in patients with a specific type of lung cancer that has spread or come back. Brigatinib blocks growth signals in cancer cells, while bevacizumab blocks the tumor's blood supply. The goal is to find the best dose and see how well these drugs work together.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments or investigational drugs within a specific time before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Bevacizumab (Avastin) for lung cancer?

Research shows that Bevacizumab, when combined with chemotherapy, improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC). Studies have demonstrated its effectiveness in improving survival rates in this setting. ^{1 2 3 4 5}

Is the combination of Brigatinib and Bevacizumab safe for humans?

Bevacizumab, also known as Avastin, has been used safely in combination with other treatments for non-small cell lung cancer, with common side effects including manageable high blood pressure and protein in the urine. Proper patient selection can reduce the risk of serious side effects like pulmonary bleeding. ^{1 6 7 8 9}

How is the drug Brigatinib + Bevacizumab unique for lung cancer treatment?

The combination of Brigatinib and Bevacizumab is unique because it pairs Brigatinib, a targeted therapy that inhibits specific cancer cell growth signals, with Bevacizumab, which blocks the blood supply to tumors. This dual approach may offer a novel way to treat lung cancer by attacking the cancer cells directly and cutting off their nutrient supply. ^{1 2 4 6 8}

Research Team

Victoria Villaflor, Dr

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with ALK-rearranged non-small cell lung cancer that's advanced, spread elsewhere, or returned after treatment. They must have tried ALK-targeted therapy before and still show signs of the disease. Participants need to be in fairly good health overall, understand the study, agree to use contraception, and not have had certain treatments or surgeries recently.

Inclusion Criteria

My cancer progressed despite treatment targeting ALK.

Patients must meet criteria for appropriate contraception

My organs and bone marrow are functioning well.

Exclusion Criteria

I have not had major surgery in the last 30 days.

I have not had a recent pulmonary embolism or untreated deep vein thrombosis in the last 3 months.

I don't have any other cancers that are likely to worsen within a year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive brigatinib orally once daily and bevacizumab intravenously, with cycles repeating every 21 days in the absence of disease progression or unacceptable toxicity

Up to 3 years

Cycle 1: 1 visit (in-person), Subsequent cycles: 1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Follow-up at 30 days, 3, 6, 9, and 12 months, then every 6 months

Treatment Details

Interventions

• Bevacizumab
• Brigatinib

Trial Overview Researchers are testing brigatinib combined with bevacizumab to see how well they work together against this type of lung cancer. Brigatinib targets enzymes needed by cancer cells to grow while bevacizumab aims to stop these cells from spreading.

Participant Groups

Group I: Treatment (brigatinib, bevacizumab) Experimental Treatment 2 Interventions

Patients receive brigatinib PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive bevacizumab IV on day 8 of cycle 1 and day 1 of subsequent cycles. Starting cycle 2, cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a phase III trial involving 1,043 patients with advanced nonsquamous non-small-cell lung cancer, the combination of bevacizumab with cisplatin and gemcitabine significantly improved progression-free survival (PFS) compared to placebo, with hazard ratios of 0.75 for low-dose and 0.82 for high-dose bevacizumab.

The treatment also resulted in higher objective response rates (34.1% for low-dose and 30.4% for high-dose bevacizumab) compared to placebo (20.1%), while maintaining a similar incidence of serious adverse events across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. Reck, M., von Pawel, J., Zatloukal, P., et al.[2022]

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]

Combining bevacizumab with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) significantly prolongs progression-free survival (PFS) and increases the objective response rate (ORR) in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of five randomized controlled trials involving 1301 articles.

However, this combination treatment does not significantly improve overall survival (OS) and is associated with an increased risk of serious adverse events, indicating a need for careful consideration of safety when using this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab combined with EGFR-TKIs in advanced non-small cell lung cancer: A meta-analysis. Yang, Y., Wang, L., Li, X., et al.[2022]

References

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

First-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer : analysis of the Italian patients enrolled in the SAiL study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients. [2018]

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

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (WJOG 5910L). [2021]

6. Austria pubmed.ncbi.nlm.nih.gov

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

7. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab combined with EGFR-TKIs in advanced non-small cell lung cancer: A meta-analysis. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Gefitinib Plus Bevacizumab vs. Gefitinib Alone for EGFR Mutant Non-squamous Non-small Cell Lung Cancer. [2020]

9. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety of bevacizumab biosimilar and original bevacizumab in non-squamous non-small cell lung cancer: a systematic review and meta-analysis. [2022]