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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04871282




Registration number
NCT04871282
Ethics application status
Date submitted
23/04/2021
Date registered
4/05/2021

Titles & IDs
Public title
A Study of AL102 in Patients With Progressing Desmoid Tumors
Scientific title
RINGSIDE: A Phase 2/3, Randomized, Multicenter Study to Evaluate AL102 in Patients With Progressing Desmoid Tumors
Secondary ID [1] 0 0
AL-DES-01
Universal Trial Number (UTN)
Trial acronym
RINGSIDE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Desmoid 0 0
Desmoid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AL102
Other interventions - Placebo

Experimental: Part A Main Study 1.2 mg daily - AL102 1.2 mg

Experimental: Part A Main Study 2 mg Intermittent - AL102 2 mg

Experimental: Part A Main Study 4 mg Intermittent - AL102 4 mg

Experimental: Part B AL102 - AL102, recommended dose regimen from Part A, 1.2 mg daily

Placebo comparator: Part B Placebo - Placebo to match recommended dose regimen from Part A

Experimental: Open Label Extension - AL102, recommended dose regimen from Part A, 1.2 mg daily


Treatment: Drugs: AL102
AL102 is an inhibitor of gamma secretase-mediated Notch signaling.

Other interventions: Placebo
Placebo to match AL102
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [1] 0 0
Overall response rate
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [2] 0 0
Duration of response
Timepoint [2] 0 0
Approximately 2 years
Secondary outcome [3] 0 0
Patient reported outcome
Timepoint [3] 0 0
Approximately 2 years
Secondary outcome [4] 0 0
Patient reported outcome
Timepoint [4] 0 0
Approximately 2 years
Secondary outcome [5] 0 0
Patient reported outcome
Timepoint [5] 0 0
Approximately 2 years
Secondary outcome [6] 0 0
Patient reported outcome
Timepoint [6] 0 0
Approximately 2 years

Eligibility
Key inclusion criteria
Inclusion Criteria Part A:

1. At least 18 years of age (inclusive) at the time of signing the ICF.
2. Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent).
3. Disease progression, assessed locally by the investigator, defined as having at least one of the following:

* Unidimensional growth of desmoid tumor(s) by =10%, using the sum of the largest diameters of target lesion(s), within 18 months of the screening MRI
* Having desmoid tumor-related pain that is not adequately controlled with nonopioid medication
4. At least 1 measurable lesion amenable to volume measurements by MRI at screening (Part A only)
5. One of the following:

* Treatment naïve subjects for whom, in the opinion of the investigator, the IP is deemed appropriate, OR
* Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy)
6. Agrees to provide formalin-fixed paraffin embedded archival or fresh tumor tissue for re- confirmation of disease.
7. Must be able to swallow whole capsules with no GI condition affecting absorption; nasogastric or G-tube administration is not allowed.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Part A:

1. Diagnosed with a malignancy in the past 2 years with some exceptions.
2. Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn's disease.
3. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti- fungal therapy =7 days prior to administration of IP such as known active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at Screening.
4. Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has New York Heart Association (NYHA) Class III or IV heart failure, , symptomatic ventricular arrhythmias, sustained ventricular tachycardia, Torsade's de Pointes (TdP), the long QT syndrome, pacemaker dependence, or electrocardiographic evidence of acute ischemia.
5. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary function or uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the subject associated with his or her participation in the study.
6. Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
7. Eastern Cooperative Oncology Group (ECOG) performance status =2
8. Abnormal organ and marrow function at Screening defined as:

1. Neutrophils <1000/mm3,
2. Platelet count <100,000/mm3,
3. Hemoglobin <9 g/dL,
4. Total bilirubin >1.5x upper limit of normal (ULN) (except known Gilbert's syndrome),
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5x ULN,
6. Serum creatinine > ULN and creatinine clearance (CrCl) <60 mL/min (calculation of CrCl will be based on acceptable institution standard)
7. Uncontrolled triglyceride =Grade 2 elevations per common terminology criteria for adverse events (CTCAE) v5.0 (>300 mg/dL or >3.42 mmol/L).
9. ECG Exclusions (Part A only)

1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) =450 msec.
2. QRS duration > 110 ms
3. PR interval > 240 ms
4. Marked ST-T wave abnormalities which would make it difficult to measure the QT interval
10. Any treatments for desmoid tumors within 4 weeks prior to first dose of investigational therapy; subject must have recovered from therapy related toxicity to < CTCAE Grade 2 or clinical baseline. Therapy includes:

1. Locoregional tumor directed therapies such as major surgery, radiation, radiofrequency ablation, or cryosurgery
2. Systemic therapy including chemotherapy, biologic (anti-neoplastic agent, antibodies), TKIs (e.g., sorafenib, pazopanib, imatinib), hormonal therapy, or investigational therapy
11. Chronic NSAIDs for the treatment of desmoid tumors within 4 weeks of first dose of IP;

Inclusion Criteria Part B

1. =12 years of age (inclusive) and = 40 kg at the time of signing the ICF.
2. Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent) that has progressed by = 20% as measured by RECIST v1.1 within 12 months of the screening visit scan.
3. Evidence of measurable disease by CT/MRI scan. Measurable lesions are defined according to RECIST v1.1.
4. Subject and/or legally authorized representative (i.e. parent/guardian) must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
5. Minor subjects must be capable of giving written assent as appropriate per the applicable age (per local regulatory requirements).

For all other inclusion criteria refer to Part A inclusion criteria.

Exclusion Criteria Part B The subjects must be excluded from participating in the study if they meet any of the exclusion criteria for Part A, except where otherwise noted.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/02/2025
Actual
Sample size
Target
192
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Mannheim
Country [19] 0 0
Israel
State/province [19] 0 0
Ashkelon
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Israel
State/province [21] 0 0
Jerusalem
Country [22] 0 0
Israel
State/province [22] 0 0
Tel Aviv
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Italy
State/province [25] 0 0
Rome
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Netherlands
State/province [27] 0 0
Amsterdam
Country [28] 0 0
Netherlands
State/province [28] 0 0
Leiden
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Poland
State/province [30] 0 0
Warsaw
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Zaragoza
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Scotland
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Cambridge
Country [36] 0 0
United Kingdom
State/province [36] 0 0
London
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ayala Pharmaceuticals, Inc,
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mrinal Gounder, MD
Address 0 0
MSKCC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04871282