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A Study of AL102 in Patients With Progressing Desmoid Tumors (RINGSIDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04871282
Recruitment Status : Recruiting
First Posted : May 4, 2021
Last Update Posted : June 10, 2022
Sponsor:
Information provided by (Responsible Party):
Ayala Pharmaceuticals, Inc,

Tracking Information
First Submitted Date  ICMJE April 23, 2021
First Posted Date  ICMJE May 4, 2021
Last Update Posted Date June 10, 2022
Actual Study Start Date  ICMJE March 30, 2021
Estimated Primary Completion Date January 12, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2021)
Progression free survival [ Time Frame: Approximately 2 years ]
Progression free survival (PFS) as defined as the time from randomization until the date of assessment of progression (as assessed by BICR based on RECIST v1.1) or death by any cause
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2021)
  • Overall response rate [ Time Frame: Approximately 2 years ]
    Overall response rate (ORR) defined as the proportion of subjects with ORR (CR and PR) by BICR based on RECIST v1.1.
  • Duration of response [ Time Frame: Approximately 2 years ]
    Duration of response defined by the time from CR or PR (by BICR based on RECIST v1.1) until the earlier of the first documentation of disease progression or death from any cause.
  • Patient reported outcome [ Time Frame: Approximately 2 years ]
    Change from baseline in quality of life as measured by GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Symptom Scale and Impact Scale (GODDESS)
  • Patient reported outcome [ Time Frame: Approximately 2 years ]
    Change from baseline in quality of life as measured by Patient-reported outcomes measurement information system (PROMIS) Physical Function
  • Patient reported outcome [ Time Frame: Approximately 2 years ]
    Change from baseline in quality of life as measured by EuroQol 5-dimensional questionnaire(EQ-5D)
  • Patient reported outcome [ Time Frame: Approximately 2 years ]
    Change from baseline in pain assessment using brief pain inventory (BPI) short form
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of AL102 in Patients With Progressing Desmoid Tumors
Official Title  ICMJE RINGSIDE: A Phase 2/3, Randomized, Multicenter Study to Evaluate AL102 in Patients With Progressing Desmoid Tumors
Brief Summary The current study is designed to evaluate the efficacy and safety of AL102 in patients with progressive desmoid tumors.
Detailed Description This is a Phase 2/3, randomized study in subjects with progressive desmoid tumors consisting of 2 parts. Part A is an open-label, dose regimen finding study; Part B is a double blind, placebo-controlled study utilizing the dose regimen selected in Part A.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Desmoid
  • Desmoid Tumor
Intervention  ICMJE
  • Drug: AL102
    AL102 is an inhibitor of gamma secretase-mediated Notch signaling.
  • Other: Placebo
    Placebo to match AL102
Study Arms  ICMJE
  • Experimental: Part A Main Study 1.2 mg daily
    AL102 1.2 mg
    Intervention: Drug: AL102
  • Experimental: Part A Main Study 2 mg Intermittent
    AL102 2 mg
    Intervention: Drug: AL102
  • Experimental: Part A Main Study 4 mg Intermittent
    AL102 4 mg
    Intervention: Drug: AL102
  • Experimental: Part B AL102
    AL102, recommended dose regimen from Part A
    Intervention: Drug: AL102
  • Placebo Comparator: Part B Placebo
    Placebo to match recommended dose regimen from Part A
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2021)
192
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 21, 2025
Estimated Primary Completion Date January 12, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jason Kaplan, MD +1-857-444-0553 clinicaltrials@ayalapharma.com
Contact: Johnathan Yovell, MD clinicaltrials@ayalapharma.com
Listed Location Countries  ICMJE Australia,   Israel,   Korea, Republic of,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04871282
Other Study ID Numbers  ICMJE AL-DES-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Ayala Pharmaceuticals, Inc,
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Ayala Pharmaceuticals, Inc,
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mrinal Gounder, MD MSKCC
PRS Account Ayala Pharmaceuticals, Inc,
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP