What side effects are associated with this type of intervention?

Common side effects of treatments for Adenoid Cystic Carcinoma, particularly those targeting the NOTCH pathway like AL101, include fatigue, nausea, diarrhea, and skin reactions. Patients may also experience gastrointestinal issues, liver enzyme abnormalities, and hematologic effects such as anemia or thrombocytopenia. These side effects are typical of therapies that block enzymes needed for cell growth.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Adenoid Cystic Carcinoma (ACC) that target the NOTCH pathway or block enzymes needed for cell growth, similar to AL101. However, investigational approaches like AL101 are being studied for their potential to control ACC by targeting NOTCH pathway activation. Broader treatment strategies for ACC often involve surgery, radiation, and various chemotherapeutic agents, but targeted therapies specifically for NOTCH pathway activation are still under clinical investigation.

What other types of research exist?

Promising novel alternatives to AL101 for Adenoid Cystic Carcinoma patients include investigational agents targeting the NOTCH pathway, such as gamma-secretase inhibitors. Additionally, therapies targeting other critical pathways involved in ACC, such as PI3K inhibitors, mTOR inhibitors, and CDK4/6 inhibitors, may also be considered. Clinical trials exploring these agents could provide new treatment options in 2024.

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Notch Inhibitor

AL101 Before Surgery for Adenoid Cystic Carcinoma

Phase 1

Recruiting

Led By Renata Ferrarotto

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Creatinine clearance < 40 mL/min (Calculation of creatinine clearance [CrCl] will be based on acceptable institution standard)

Evidence of NOTCH1 pathway activation as determined by NICD1 IHC nuclear staining in >= 70% of tumor cells

Must not have

Prior treatment with gamma-secretase inhibitor

Female subjects who are pregnant or breast-feeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effects of AL101, a drug given through an IV drip, on patients with notch activated adenoid cystic cancer. The drug aims to stop the cancer cells from growing by blocking necessary enzymes. The goal is to see if AL101 can help control this specific type of cancer before surgery.

Who is the study for?

Adults with adenoid cystic carcinoma showing NOTCH1 pathway activation, who can consent to treatment and follow study rules. They must have a tumor that can be surgically removed and agree to use two forms of contraception if they're able to conceive. People with severe medical conditions, uncontrolled infections, or recent treatments for other cancers are excluded.

What is being tested?

The trial is testing AL101's effectiveness when given before surgery in patients with notch activated adenoid cystic cancer. It aims to see if AL101 can halt tumor growth by inhibiting certain enzymes needed for cell proliferation.

What are the potential side effects?

Possible side effects of AL101 may include reactions at the infusion site, increased risk of infection due to immune system suppression, liver enzyme alterations leading to potential liver damage, blood clotting issues such as bleeding diathesis or coagulopathy, and gastrointestinal disturbances.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by creatinine clearance, is below 40 mL/min.

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My cancer shows high NOTCH1 activity.

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I am willing to have a biopsy to provide tumor samples.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

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My cancer is confirmed as adenoid cystic carcinoma.

Exclusion Criteria

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

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I have been treated with a gamma-secretase inhibitor before.

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I am not pregnant or breastfeeding.

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I do not have a bleeding disorder that isn't managed by medication.

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I do not have an active infection needing treatment within the last week.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Changes in NICD1 levels

Incidence of adverse events

Secondary study objectives

Overall response rate

Side effects data

From 2022 Phase 2 trial • 87 Patients • NCT03691207

79%

Diarrhoea

60%

Fatigue

45%

Nausea

43%

Hypophosphataemia

38%

Cough

33%

Epistaxis

31%

Vomiting

31%

Dry mouth

29%

Decreased appetite

29%

Insomnia

26%

Weight decreased

24%

Constipation

21%

Dysgeusia

19%

Dyspnoea

19%

Rash

19%

Dermatitis acneiform

17%

Rash maculo-papular

17%

Alopecia

17%

Stomatitis

17%

Asthenia

17%

Dry skin

14%

Hypokalaemia

12%

Dysphonia

12%

Oropharyngeal pain

12%

Mucosal inflammation

12%

Hypocalcaemia

12%

Pruritus

10%

Dyspepsia

10%

Productive cough

10%

Oral pain

10%

Dehydration

10%

Hyperglycaemia

10%

Headache

10%

Dizziness

10%

Pneumonia

10%

Aspartate aminotransferase increased

10%

Alanine aminotransferase increased

10%

Platelet count decreased

10%

Back pain

10%

Dry eye

10%

Hypertension

10%

Anaemia

Gastrooesophageal reflux disease

Dysphagia

Abdominal pain upper

Hypoxia

Pyrexia

Oedema peripheral

Facial pain

Swelling face

Palmar-plantar erythrodysaesthesia syndrome

Erythema

Night sweats

Neuralgia

Urinary tract infection

Oral candidiasis

Candida infection

Neutrophil count increased

Arthralgia

Vision blurred

Infusion related reaction

Pneumonia aspiration

Cardiac arrest

Nasal dryness

Skin lesion

Anxiety

Depression

Sepsis

Clostridium difficile colitis

Abdominal infection

Anorectal infection

Campylobacter sepsis

Cellulitis

Pneumonia pseudomonal

Streptococcal bacteraemia

Respiratory failure

Acute respiratory distress syndrome

Bronchial obstruction

Eosinophilic pneumonia

Haemoptysis

Pleural effusion

Pneumonitis

Brain cancer metastatic

Brain neoplasm

Metastases to central nervous system

Squamous cell carcinoma

Encephalopathy

Femoral neck fracture

Ejection fraction decreased

Drug-induced liver injury

Hepatobiliary disease

Pathological fracture

Vasculitis

Abdominal pain

Nasal congestion

Upper-airway cough syndrome

Chills

Hyponatraemia

Musculoskeletal pain

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 2 - AL101 6mg

Cohort 1 - AL101 4mg

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 (AL101)Experimental Treatment2 Interventions

Patients receive AL101 IV over 60 minutes QW for 6-8 weeks in the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the last infusion of AL101, patients undergo surgery per standard of care. Patients may continue AL101 after surgery at the discretion of the study doctor.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AL101

2018

Completed Phase 2

~180

Therapeutic Conventional Surgery

2005

Completed Phase 3

~9870

0 / 10Eligibility 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

The most common treatments for Adenoid Cystic Carcinoma (ACC) often target specific pathways critical for tumor growth and survival. AL101, for instance, blocks enzymes needed for cell growth by targeting the NOTCH pathway activation, which is significant because NOTCH signaling is implicated in the proliferation and survival of ACC cells. Similarly, AEE788 inhibits the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR), leading to growth inhibition and apoptosis of ACC cells. These targeted therapies are important for ACC patients as they disrupt the molecular mechanisms that drive tumor growth, potentially leading to more effective disease control and improved patient outcomes.

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