Clinical trial NCT04871282: A Study of AL102 in Patients With Progressing Desmoid Tumors
Official title: RINGSIDE: A Phase 2/3, Randomized, Multicenter Study to Evaluate AL102 in Patients With Progressing Desmoid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Desmoid
Desmoid Tumor
Keywords: RINGSIDE
Lead sponsor: Immunome, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-04
Enrollment: 198
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. Phase2/Part A is an open-label, dose regimen finding study; Phase3/Part B is a double blind, placebo-controlled study and Open Label Extension utilizing the dose regimen selected in Phase2/Part A.

Eligibility criteria: Inclusion Criteria Part A:

1. At least 18 years of age (inclusive) at the time of signing the informed consent form (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.

Primary outcomes:
measure: Progression free survival
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Overall response rate
timeFrame: Approximately 2 years
measure: Change in Tumor Volume
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
measure: Progression Free Survival
timeFrame: Approximately 2 years
measure: Patient reported outcome
timeFrame: Approximately 2 years
measure: Safety and Tolerability
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Pheonix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Santa Monica
country: United States
facility: University of California at Los Angeles Hematology/Oncology
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Jefferson City
country: United States
facility: Jefferson City Medical Group
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Hillman Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: UTSW Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Gent
country: Belgium
facility: Universitair Ziekenhuis
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Mannheim
country: Germany
facility: Mannheim university medical center
city: Ashkelon
country: Israel
facility: Oncology Institute Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam MC
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: IRCCS Istituto Ortopedico Rizzoli
city: Milano
country: Italy
facility: IRCCS Fondazione Istituto Nazionale dei Tumori
city: Rome
country: Italy
facility: Campus Bio-Medico University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie National Research Institute of Oncology
city: Barcelona
country: Spain
facility: Vall d´Hebrón University Hospital
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology (ICO)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: MSKCC
name: Mrinal Gounder, MD
role: PRINCIPAL_INVESTIGATOR
References: