A study of investigational medicinal product AL101 in adults who have adenoid cystic carcinoma, and a specific genetic alteration in a gene called Notch, that has come back or did not get better with a previous therapy
- Conditions
- Adenoid cystic carcinomaMedDRA version: 20.0Level: PTClassification code 10053231Term: Adenoid cystic carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000309-64-FR
- Lead Sponsor
- Ayala Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
1. Age = 18 years old.
2. Histologically confirmed ACC with known NOTCH 1/2/3/4 activating mutation that is recurrent or metastatic, not amenable to potentially curative surgery or radiotherapy.
3. Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
4. Patients must have FFPE tissue available (please refer to laboratory manual for number of slides required). Archived (within 3 years) or fresh core or punch needle biopsied are acceptable.
5. Must have at least 1 target lesion that is measurable per RECIST v1.1 for patients with nodal or visceral metastasis. Patients with bone exclusive disease will also be eligible if bone lesions are evaluable by CT or MRI as per modified MDA Criteria.
6. Resolution of clinically significant toxicities related to prior therapy to CTCAE v5.0 = Grade 1, except for sensory neuropathy with resolution to = Grade 2 and alopecia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 6
1. Diagnosed with a malignancy in the past 2 years.
2. Current or recent gastrointestinal disease. Nonchronic conditions that are completely resolved for at least 2 weeks prior to starting study drug are not exclusionary
3. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy =7 days prior to administration of study drug at Screening.
4. Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases as well as those with previously treated CNS metastases are eligible for enrolment in the study if at least four weeks has elapsed since last whole brain radiation treatment or at least two weeks has elapsed since last focal radiation treatment, steroid therapy is not required, and the patient is deemed clinically stable by the Investigator.
5. Unstable or severe uncontrolled medical condition or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgement, increase the risk to the patient associated with his or her participation in the study.
6. Female patients who are pregnant or breastfeeding.
7. Completed palliative radiation therapy < 7 days prior to initiating study drug.
8. Prior treatment with gamma secretase inhibitors. .
9. Patients treated with a nucleoside analogue within 6 months prior to administration of study drug.
10. Last chemotherapy, biologic, or investigational therapy agent <4 weeks or 5 half-lives (whichever is shorter) prior to initiating study drug; 6 weeks if the last regimen included BCNU or mitomycin C.
11. Eastern Cooperative Oncology Group (ECOG) performance status =2.
12. Abnormal organ and marrow function
13. Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
14. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =480 msec.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the clinical activity of AL101 using radiographic assessments and RECIST v1.1 in ACC patients with activating Notch mutations;Secondary Objective: To confirm safety and tolerability of AL101 in ACC patients with activating Notch mutations<br>To obtain a set of population parameters and to identify covariates that affect systemic exposure to AL101 and metabolite(s);Primary end point(s): Objective response rate (ORR; complete response [CR] and partial response [PR]) by RECIST v1.1 [ Time Frame: Up to 36 month ];Timepoint(s) of evaluation of this end point: Imaging and radiologic evaluation will be performed every 8 weeks during treatment period and then at 3 month intervals during long-term follow-up
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Frequency, duration and severity of adverse events (AEs) and serious adverse events (SAEs); [ Time Frame: Up to 36 month ];Timepoint(s) of evaluation of this end point: Safety evaluations will be performed on D1, D8, D15 and D22 of each treatment cycle and 30 days post last study drug administration