Adenoid Cystic CarcinomaPhase 2ACCURACYNCT03691207
A Study Of AL101In Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations
A Phase 2 study testing AL101 in people with Adenoid Cystic Carcinoma, run by Ayala Pharmaceuticals, Inc, at 17 sites in 6 countries.
Trial summary
This is a Phase 2, non comparative, open label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenoid Cystic Carcinoma
- What is being tested?
- AL101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 14 Dec 2018to 2 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed Adenoid Cystic Carcinoma with known NOTCH 1/2/3/4 activating mutation that is recurrent or metastatic, not amenable to potentially curative surgery or radiotherapy.
- Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
- Patients must have Formalin-fixed, Paraffin-embedded tissue available .
- Must have at least 1 target lesion that is measurable for patients with nodal or visceral metastasis.
Who cannot join
- Diagnosed with a malignancy other than ACC in the past 2 years.
- Uncontrolled, Active Infection
- Gastrointestinal (GI) disease with increased risk of diarrhea [e.g. inflammatory bowel disease (IBD)]
- Symptomatic central nervous system (CNS) metastases.
- Unstable or severe uncontrolled medical condition
- Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
- Abnormal organ and marrow function
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
United States10 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Massachusetts General Hospital
Boston, Massachusetts, 02114
MD Anderson Cancer Center
Houston, Texas, 77030
USC Norris Comprehensive Cancer center
Los Angeles, California, 90033
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic Hospital
Rochester, Minnesota, 55902
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Canada3 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Hamilton Health Sciences Juravinski Cancer Centre
Hamilton, Ontario, L8V 1C3
London Health Sciences Center
London, Ontario, N6A 5W9
United Kingdom1 site
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations
This is a Phase 2, non comparative, open label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.
Read the detailed description
This is a Phase 2, non-comparative, open-label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.
The study includes 2 cohorts, ran in a sequential fashion:
Cohort 1 - AL101 4 mg once weekly (QW) intravenously (IV) Cohort 2 - AL101 6 mg QW IV
- Conditions
- Adenoid Cystic Carcinoma
- Being tested
- AL101
- Medical subject headings
- Carcinoma, Adenoid Cystic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL101Drug
Also called BMS 906024
AL101 is a small-molecule that inhibits gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway by releasing the Notch intracellular domain (NICD) of all four Notch receptors from the membrane.
In patients with aberrant Notch signaling, AL101 may inhibit Notch signaling and potentially impede tumor growth.The drug is administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| SINGLE-ARM | Experimental | AL101 is an inhibitor of gamma secretase-mediated Notch signaling. Receives: Drug: AL101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR is defined as partial response (PR) + complete response (CR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for target lesions assessed by MRI.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 3 years and 7 months
Secondary outcomes (2)
Clinical Benefit Response Rate (CBR)
Clinical benefit response rate (CBR) is defined as complete response (CR) + partial response (PR) + stable disease (SD) by investigator review based on RECIST v1.1 for target lesions assessed by MRI.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Stable Disease (SD): Neither sufficient shrinkage (at least 30%) to qualify for PR nor sufficient increase (more than 20%) to qualify for PD, taking as reference the smallest sum diameters.
Measured: 3 years and 7 months
Overall Survival
Overall survival is defined at the time from first infusion of investigational product to death due to any cause. Subjects with no documentation of death were censored at the last known date known to be alive.
Measured: 3 years and 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start14 Dec 2018
- Primary completion15 Jul 2022
- Study completion2 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenoid Cystic CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ayala Pharmaceuticals, Inc,
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03691207
- Sponsor's protocol ID
- AL-ACC-01
- Acronym
- ACCURACY
- Status last verified
- Jan 2024
- First submitted
- 22 Sep 2018
- Last updated
- 31 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations
- ClinicalTrials.gov ID
- NCT03691207
- Acronym / sponsor ID
- ACCURACY / AL-ACC-01
- Conditions
- Adenoid Cystic Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Ayala Pharmaceuticals, Inc,Industry (pharma, biotech, devices)
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 15 Jul 2022 (actual)
- Study completion
- 2 Dec 2022 (actual)
- First posted
- 1 Oct 2018 (actual)
- Results
- Posted 31 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, non comparative, open label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.
Detailed description
This is a Phase 2, non-comparative, open-label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.
The study includes 2 cohorts, ran in a sequential fashion:
Cohort 1 - AL101 4 mg once weekly (QW) intravenously (IV) Cohort 2 - AL101 6 mg QW IV
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label
| Arm | Type | Receives |
|---|---|---|
| SINGLE-ARM | Experimental | Drug: AL101AL101 is an inhibitor of gamma secretase-mediated Notch signaling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed Adenoid Cystic Carcinoma with known NOTCH 1/2/3/4 activating mutation that is recurrent or metastatic, not amenable to potentially curative surgery or radiotherapy.
- Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
- Patients must have Formalin-fixed, Paraffin-embedded tissue available .
- Must have at least 1 target lesion that is measurable for patients with nodal or visceral metastasis.
Key exclusion criteria (7 listed)
- Diagnosed with a malignancy other than ACC in the past 2 years.
- Uncontrolled, Active Infection
- Gastrointestinal (GI) disease with increased risk of diarrhea [e.g. inflammatory bowel disease (IBD)]
- Symptomatic central nervous system (CNS) metastases.
- Unstable or severe uncontrolled medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AL101Also: BMS 906024AL101 is a small-molecule that inhibits gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway by releasing the Notch intracellular domain (NICD) of all four Notch receptors from the membrane. In patients with aberrant Notch signaling, AL101 may inhibit Notch signaling and potentially impede tumor growth.The drug is administered intravenously | Drug | SINGLE-ARM |
Primary outcome
Overall Response Rate (ORR)
Time frame: 3 years and 7 months
ORR is defined as partial response (PR) + complete response (CR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for target lesions assessed by MRI. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
2 secondary outcomes
Clinical Benefit Response Rate (CBR)
Time frame: 3 years and 7 months
Overall Survival
Time frame: 3 years and 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AL101 in people with Adenoid Cystic Carcinoma, run by Ayala Pharmaceuticals, Inc, at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada, France, Israel, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: 3 years and 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.