Brigatinib + Bevacizumab for Lung Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining brigatinib and bevacizumab (Avastin) for individuals with ALK-rearranged non-small cell lung cancer. Researchers aim to determine the optimal dose and monitor side effects while assessing whether these drugs can halt cancer growth and spread. The trial seeks participants whose lung cancer has spread or returned after ALK-directed therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that brigatinib and bevacizumab are likely to be safe for humans?

Research shows that using brigatinib and bevacizumab together is generally safe for treating certain cancers. Although direct research on this specific combination is lacking, brigatinib has been approved for some lung cancers, indicating its safety. Bevacizumab, a lab-made protein, has been widely used in cancer treatments, often alongside other drugs.

In a study where bevacizumab was combined with a similar drug, alectinib, for a type of lung cancer, the combination proved safe. This suggests that bevacizumab does not cause many additional side effects when used with drugs like brigatinib. However, since this is an early-stage trial, the safety of using brigatinib and bevacizumab together is still under investigation, and participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of brigatinib and bevacizumab for lung cancer because it offers a unique approach compared to existing treatments. Brigatinib is a next-generation ALK inhibitor, which means it specifically targets and blocks the activity of proteins involved in cancer cell growth that other treatments might miss. Bevacizumab, on the other hand, is an angiogenesis inhibitor, which works by cutting off the blood supply that tumors need to grow. By combining these two mechanisms, this treatment has the potential to be more effective at slowing down or stopping tumor growth than current standard options, which typically focus on just one pathway.

What evidence suggests that brigatinib and bevacizumab might be effective for lung cancer?

This trial will evaluate the combination of brigatinib and bevacizumab for treating ALK-positive non-small cell lung cancer (NSCLC). Studies have shown that brigatinib can benefit patients with this specific type of lung cancer, outperforming crizotinib. Bevacizumab, a medicine that blocks the blood vessels tumors need, can stop cancer growth. When combined with chemotherapy, bevacizumab has improved treatment outcomes for NSCLC. Although the effectiveness of using brigatinib and bevacizumab together remains uncertain, their individual success offers hope for treating ALK-rearranged NSCLC. ^{2 6 7 8 9}

Who Is on the Research Team?

Victoria Villaflor, Dr

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-08726

Brigatinib and Bevacizumab for the Treatment of ALK ... It is not yet known if brigatinib and bevacizumab will work better in treating patients with ALK-rearranged non-small cell lung cancer. Eligibility Criteria ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468605/

Real World Data on the Efficacy of Brigatinib in ALK-Positive ... Results of the ALTA 1L study showed superior outcomes for patients with ALK-positive NSCLC treated with brigatinib compared to patients treated with crizotinib.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04227028?cond=%22Lung%20Non-Small%20Cell%20Carcinoma%22&intr=%22endothelial%20growth%20factors%22&viewType=Table&rank=5

Brigatinib and Bevacizumab for the Treatment of ALK ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842822001275

Association between bevacizumab with cancer drug ... This study aimed to determine interstitial lung disease (ILD) incidences in patients receiving cancer drug therapies with or without bevacizumab treatment.

5. cancerci.biomedcentral.com cancerci.biomedcentral.com/articles/10.1186/s12935-020-01639-4

A comparison of the efficacy of antiangiogenic agents ... In terms of ORR, bevacizumab combined with chemotheray may have a better effect for the treatment of NSCLC; and in terms of OS and PFS, Endostar ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8666648/

Safety and activity of alectinib plus bevacizumab in patients ... Alectinib plus bevacizumab is safe in patients with advanced ALK-rearranged non-small-cell lung cancer. •. Bevacizumab combined with alectinib does not increase ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04227028

Brigatinib and Bevacizumab for the Treatment of ALK ... This phase Ib trial studies the side effects and best dose of brigatinib and how well it works with bevacizumab in treating patients with ALK-rearranged ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)41701-6/pdf

HS-110 and nivolumab Conclusions: MYL is equivalent to Avastin, given in combination with CP, as measured by ORR. Other efficacy endpoints, safety and immunogenicity were comparable ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22173662/

safety of avastin in lung trial (MO19390) Serious AEs were reported in 45.3 and 34.7% of elderly and younger patients, respectively. Median OS was similar in elderly and younger patients (14.6 months in ...