A Study Of AL101In Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations

Adenoid Cystic Carcinoma Clinical Trial

— ACCURACY  

Official title:

A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03691207
• Other study ID #: AL-ACC-01
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2018
• Est. completion date: December 2, 2022

Study information

• Verified date: January 2024
• Source: Ayala Pharmaceuticals, Inc,
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: December 2, 2022
• Est. primary completion date: July 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.

3. Patients must have Formalin-fixed, Paraffin-embedded tissue available .

4. Must have at least 1 target lesion that is measurable for patients with nodal or visceral metastasis.

Exclusion Criteria:

1. Diagnosed with a malignancy other than ACC in the past 2 years.

2. Uncontrolled, Active Infection

3. Gastrointestinal (GI) disease with increased risk of diarrhea [e.g. inflammatory bowel disease (IBD)]

4. Symptomatic central nervous system (CNS) metastases.

5. Unstable or severe uncontrolled medical condition

6. Eastern Cooperative Oncology Group (ECOG) performance status =2.

7. Abnormal organ and marrow function

Related Conditions & MeSH terms

• Adenoid Cystic Carcinoma
• Carcinoma
• Carcinoma, Adenoid Cystic

Intervention

Drug:
• AL101
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

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Hamilton Health Sciences Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Center	London	Ontario
France	Institut Gustave Roussy	Villejuif
Israel	Rabin Medical center	Petah Tikva
Netherlands	Radboud University	Nijmegen
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	USC Norris Comprehensive Cancer center	Los Angeles	California
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic Hospital	Rochester	Minnesota
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ayala Pharmaceuticals, Inc,

Countries where clinical trial is conducted

United States,  Canada,  France,  Israel,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 years and 7 months
Secondary	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.	3 years and 7 months
Secondary	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.	3 years and 5 months