Jefferson City, Missouri 65109

  • Desmoid Tumor

Purpose:

The current study is designed to evaluate the efficacy and safety of AL102 in patients with progressive desmoid tumors.


Study summary:

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.


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) that has progressed by ≥ 20% as measured by RECIST v1.1 within 12 months of the screening visit scan. 3. At least 1 measurable lesion amenable to volume measurements by MRI at screening (Part A only) 4. One of the following: - Treatment naïve subjects whose disease is not amenable to surgery without the risk of significant morbidity; OR - Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy). 5. A desmoid tumor in which continued progressive disease will not result in immediate significant risk to the subject. 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. 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. Evidence of measurable disease by CT/MRI scan. Measurable lesions are defined according to RECIST v1.1. 3. 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. 4. 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.


NCT ID:

NCT04871282


Primary Contact:

Jason Kaplan, MD
Phone: +1-857-444-0553
Email: clinicaltrials@ayalapharma.com


Backup Contact:

N/A


Location Contact:

Jefferson City, Missouri 65109
United States

Shadi Haddadin, MD
Phone: 573-556-7718

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: August 04, 2021

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