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Notch Inhibitor
AL101 Before Surgery for Adenoid Cystic Carcinoma
Phase 1
Waitlist Available
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 belowSelect...
My kidney function, measured by creatinine clearance, is below 40 mL/min.
Select...
My cancer shows high NOTCH1 activity.
Select...
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:Select...
I have been treated with a gamma-secretase inhibitor before.
Select...
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
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 • NCT0369120779%
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
7%
Gastrooesophageal reflux disease
7%
Dysphagia
7%
Abdominal pain upper
7%
Hypoxia
7%
Pyrexia
7%
Oedema peripheral
7%
Facial pain
7%
Swelling face
7%
Palmar-plantar erythrodysaesthesia syndrome
7%
Erythema
7%
Night sweats
7%
Neuralgia
7%
Urinary tract infection
7%
Oral candidiasis
7%
Candida infection
7%
Neutrophil count increased
7%
Arthralgia
7%
Vision blurred
7%
Infusion related reaction
5%
Pneumonia aspiration
5%
Cardiac arrest
5%
Nasal dryness
5%
Skin lesion
5%
Anxiety
5%
Depression
2%
Sepsis
2%
Clostridium difficile colitis
2%
Abdominal infection
2%
Anorectal infection
2%
Campylobacter sepsis
2%
Cellulitis
2%
Pneumonia pseudomonal
2%
Streptococcal bacteraemia
2%
Respiratory failure
2%
Acute respiratory distress syndrome
2%
Bronchial obstruction
2%
Eosinophilic pneumonia
2%
Haemoptysis
2%
Pleural effusion
2%
Pneumonitis
2%
Brain cancer metastatic
2%
Brain neoplasm
2%
Metastases to central nervous system
2%
Squamous cell carcinoma
2%
Encephalopathy
2%
Femoral neck fracture
2%
Ejection fraction decreased
2%
Drug-induced liver injury
2%
Hepatobiliary disease
2%
Pathological fracture
2%
Vasculitis
2%
Abdominal pain
2%
Nasal congestion
2%
Upper-airway cough syndrome
2%
Chills
2%
Hyponatraemia
2%
Musculoskeletal pain
100%
80%
60%
40%
20%
0%
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
~9890
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.
Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells.Effects of Jiazhu decoction in combination with cyclophosphamide on breast cancer in mice.IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence.
Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells.Effects of Jiazhu decoction in combination with cyclophosphamide on breast cancer in mice.IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence.
Find a Location
Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
3,070 Previous Clinical Trials
1,802,794 Total Patients Enrolled
Renata FerrarottoPrincipal InvestigatorM.D. Anderson Cancer Center
6 Previous Clinical Trials
159 Total Patients Enrolled
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- You are capable of giving informed consent.You have had an allergic reaction or are allergic to the ingredients in the investigational product.My doctor believes my cancer can be surgically removed, either to try to cure it or to control its spread.I had cancer treatment at least 4 weeks ago for a local recurrence.My kidney function, measured by creatinine clearance, is below 40 mL/min.I have been treated with a gamma-secretase inhibitor before.I had cancer before, but it was treated, and I've been cancer-free for over 2 years.My cancer shows high NOTCH1 activity.I am willing to have a biopsy to provide tumor samples.I am fully active or restricted in physically strenuous activity but can do light work.I am not pregnant or breastfeeding.I agree to use contraception during and for 3 months after AL101 therapy.I have brain metastases but no current symptoms, or I've been treated and stable for at least 4 weeks.I am using two effective birth control methods while on and 90 days after AL101 therapy.I do not have ongoing stomach or bowel diseases that cause diarrhea.I am 18 years old or older.My cancer is confirmed as adenoid cystic carcinoma.I do not have a bleeding disorder that isn't managed by medication.I do not have an active infection needing treatment within the last week.
Research Study Groups:
This trial has the following groups:- Group 1: Treatment (AL101)
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.
Adenoid Cystic Carcinoma Patient Testimony for trial: Trial Name: NCT04973683 — Phase 1