What side effects are associated with this type of intervention?

Common treatments for lung cancer, such as ALK inhibitors (e.g., Brigatinib) and angiogenesis inhibitors (e.g., Bevacizumab), have specific side effects. ALK inhibitors can cause fatigue, nausea, increased liver function tests, and in some cases, more severe effects like pulmonary hemorrhage or cardiac failure. Angiogenesis inhibitors like Bevacizumab are associated with hypertension, proteinuria, bleeding, and gastrointestinal perforation. Both classes of drugs require careful monitoring due to these potential adverse effects.

What prior FDA approvals exist?

For the treatment of ALK-positive non-small cell lung cancer (NSCLC), the FDA has approved several ALK inhibitors, including alectinib, ceritinib, brigatinib, and lorlatinib. These drugs have shown clinical benefits in both treatment-naïve patients and those who have progressed after initial therapy with crizotinib. Bevacizumab, an angiogenesis inhibitor, has also been approved for use in combination with chemotherapy for advanced non-squamous NSCLC, demonstrating improved progression-free survival and overall survival in clinical trials.

What other types of research exist?

Promising alternatives to Brigatinib (ALK inhibitor) include Lorlatinib and Ceritinib, which have shown efficacy in patients with ALK-rearranged lung cancer. For Bevacizumab (angiogenesis inhibitor), other options include Ramucirumab and Apatinib, which target VEGFR pathways. Additionally, novel agents like Selpercatinib and Pralsetinib, which target RET mutations, and multitargeted kinase inhibitors like Regorafenib and Cabozantinib, are also emerging as potential treatments for lung cancer.

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Monoclonal Antibodies

Brigatinib + Bevacizumab for Lung Cancer

Phase 1

Waitlist Available

Led By Victoria M. Villaflor, M.D.

Research Sponsored by Northwestern University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have shown progression on ALK-directed therapy

Patients must have adequate organ and bone marrow function during screening

Must not have

Patients who have had major surgery within 30 days of registration, are not eligible

Patients with recent history of pulmonary embolism, or untreated deep vein thrombosis in the last 3 months are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include high blood pressure, bleeding problems, fatigue, liver issues and risks related to heart health. There might also be reactions where the drugs are infused into the body and potential harm if a participant has surgery during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer progressed despite treatment targeting ALK.

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My organs and bone marrow are functioning well.

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I have brain metastases but no symptoms, and I don't have cancer in the lining of my brain.

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My lung cancer is advanced, recurrent, or has spread and tests show ALK changes.

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I am following the required birth control guidelines.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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

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I do not have uncontrolled heart problems.

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I do not have severe lung inflammation from drugs or radiation.

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My blood pressure is under control.

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I do not have severe unresolved lung disease.

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I do not have any uncontrolled illnesses.

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I am not pregnant, planning to become pregnant, or nursing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Maximum tolerated dose

Secondary study objectives

Dose-limiting toxicities

Duration of response

Overall response rate

+2 more

Side effects data

From 2021 Phase 3 trial • 275 Patients • NCT02737501

57%

Diarrhoea

50%

Blood Creatine Phosphokinase Increased

36%

Cough

32%

Hypertension

32%

Nausea

26%

Back Pain

26%

Aspartate Aminotransferase Increased

23%

Headache

23%

Dyspnoea

23%

Alanine Aminotransferase Increased

23%

Lipase Increased

22%

Vomiting

21%

Fatigue

21%

Pruritus

20%

Arthralgia

19%

Constipation

18%

Rash

17%

Dizziness

15%

Muscle Spasms

15%

Pyrexia

13%

Upper Respiratory Tract Infection

13%

Abdominal Pain

13%

Blood Alkaline Phosphatase Increased

13%

Asthenia

12%

Decreased Appetite

11%

Dyspepsia

11%

Musculoskeletal Pain

10%

Insomnia

10%

Dermatitis Acneiform

10%

Myalgia

10%

Oedema Peripheral

10%

Blood Cholesterol Increased

10%

Oropharyngeal Pain

Productive Cough

Nasopharyngitis

Anaemia

Paraesthesia

Stomatitis

Musculoskeletal Chest Pain

Non-Cardiac Chest Pain

Abdominal Pain Upper

Urinary Tract Infection

Bradycardia

Epistaxis

Pneumonia

Pain In Extremity

Rash Erythematous

Dry Skin

Rash Maculo-Papular

Dysphonia

Electrocardiogram Qt Prolonged

Dry Mouth

Eczema

Blood Creatinine Increased

Sinus Bradycardia

Respiratory Tract Infection

Hyperglycaemia

Hypokalaemia

Hypercholesterolaemia

Vision Blurred

Blood Lactate Dehydrogenase Increased

Hypophosphataemia

Rhinorrhoea

Malaise

Depression

Dysgeusia

Influenza Like Illness

Peripheral Swelling

Gamma-Glutamyltransferase Increased

Neoplasm Progression

Neutrophil Count Decreased

Pulmonary Embolism

Pleural Effusion

Interstitial Lung Disease

Hypocalcaemia

Hypoaesthesia

Taste Disorder

Hypotension

Gastroenteritis

Transaminases Abnormal

Femoral Neck Fracture

Toxicity To Various Agents

Lower Respiratory Tract Infection

Appendicitis

Visual Impairment

Disseminated Intravascular Coagulation

Confusional State

Cerebrovascular Accident

Dysarthria

Encephalopathy

Peripheral Sensory Neuropathy

Cholestasis

Muscular Weakness

Malignant Pleural Effusion

Cancer Pain

Diffuse Large B-Cell Lymphoma

Invasive Breast Carcinoma

Lung Neoplasm Malignant

Ovarian Cancer Stage I

Neutropenia

Gout

Syncope

Seizure

Memory Impairment

Vocal Cord Paralysis

Pericardial Effusion

Cardiac Tamponade

Acute Myocardial Infarction

Angina Pectoris

Arrhythmia

Pneumonitis

Pneumonia Aspiration

Pneumothorax

Pulmonary Oedema

Dysphagia

Inguinal Hernia

Neutropenic Colitis

Oesophageal Obstruction

Cholecystitis

Bile Duct Stone

Multiple Organ Dysfunction Syndrome

Sudden Death

C-Reactive Protein Increased

Fall

Ligament Rupture

Hypoalbuminaemia

Viral Infection

Metastases To Meninges

Lung Adenocarcinoma

Squamous Cell Carcinoma Of Skin

Hypoglycaemia

Delirium

Balance Disorder

Partial Seizures

Atrial Fibrillation

Hepatocellular Injury

Acute Kidney Injury

Photopsia

Metastases To Central Nervous System

Hyperkalaemia

Cognitive Disorder

Gastric Haemorrhage

Mucosal Inflammation

Gastrooesophageal Reflux Disease

Respiratory Distress

100%

80%

60%

40%

20%

Study treatment Arm

Randomized Phase: Brigatinib 90 mg QD/180 QD

Randomized Phase: Crizotinib 250 mg BID

Crossover Phase: Brigatinib 90 mg QD/180 mg QD

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (brigatinib, bevacizumab)Experimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bevacizumab

2013

Completed Phase 4

~5540

Brigatinib

2019

Completed Phase 3

~1240

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

ALK inhibitors like Brigatinib block the activity of the ALK protein, reducing tumor growth in ALK-rearranged NSCLC. Angiogenesis inhibitors like Bevacizumab inhibit VEGF, preventing the formation of new blood vessels that tumors need to grow. These targeted therapies are crucial for effectively treating lung cancer by addressing specific mechanisms that drive tumor growth and spread.

New systemic strategies for overcoming resistance to targeted therapies in non-small cell lung cancer.Trials to Overcome Drug Resistance to EGFR and ALK Targeted Therapies - Past, Present, and Future.