Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma
- Registration Number
- NCT04979442
- Lead Sponsor
- Rain Oncology Inc
- Brief Summary
Randomized, multicenter, open-label, Phase 3 registration study designed to evaluate the safety and efficacy of milademetan compared to trabectedin in patients with unresectable (i.e., where resection is deemed to cause unacceptable morbidity or mortality) or metastatic DD liposarcoma that progressed on 1 or more prior systemic therapies, including at least 1 anthracycline-based therapy.
- Detailed Description
Approximately 160 patients will be randomly assigned in a 1:1 ratio to receive milademetan or trabectedin. Randomization will be stratified by the ECOG performance status (0 or 1) and number of prior treatments (≤ 2 or \> 2) for the patient's liposarcoma.
Patients will receive study drug (i.e., milademetan or trabectedin) until reaching unequivocal disease progression (RECIST v.1.1) as determined by the Investigator, experiencing unmanageable toxicity, or until other treatment discontinuation criteria are met. Patients may be treated beyond tumor progression if they are experiencing clinical benefit based on the assessment of the Investigator in discussion with the Medical Monitor. All patients will be followed for documentation of disease progression and survival information (i.e., date and cause of death) and subsequent treatment information (i.e., date/duration of treatment, response, and subsequent disease progression). Long-term follow-up will continue every 12 weeks (± 7 days) until the endpoint of death, the patient is lost to follow-up, or for 24 months following the final dose of study drug, whichever comes first.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 175
-
Histologically confirmed DD liposarcoma, with or without a WD component (WD/DD liposarcoma). Note: Patient must be willing to provide an archival tumor tissue sample that is ≤ 3 years old and of adequate quality or willing to provide a fresh pretreatment biopsy sample
-
Advanced unresectable (i.e., where resection is deemed to cause unacceptable morbidity or mortality) and/or metastatic WD/DD liposarcoma
-
Measurable tumor lesion(s) in accordance with RECIST version 1.1
-
Received 1 or more systemic cancer therapy regimens, including at least 1 anthracycline-based regimen, and had radiographic progressive disease (per RECIST version 1.1) within 6 months before the Screening Visit
-
Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
-
ECOG performance status of 0 or 1
-
Adequate bone marrow function:
- Platelet count ≥ 100 × 10^9/L
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1.5 × 10^9/L
-
Adequate hepatic function:
- Alanine aminotransferase and aspartate aminotransferase ≤ 3 × upper limit of normal (ULN) if no liver metastases are present; ≤ 5 × ULN if liver metastases are present
- Total bilirubin ≤ 1.5 × ULN, or ≤ 3 x ULN in the setting of Gilbert's disease
-
Prior treatment with any mouse double minute 2 (MDM2) inhibitor or trabectedin
-
Other primary malignancies that have required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured
-
Gastrointestinal conditions that could affect the absorption of milademetan, in the opinion of the Investigator
-
Uncontrolled infection within the last 7 days requiring IV antibiotics, antivirals, or antifungals
-
Known HIV infection or active Hepatitis B or C
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Untreated brain metastases. Note: Patients who require steroids for brain metastases must be on a stable or tapering dose of corticosteroids for at least 2 weeks before randomization. If applicable, patients must complete stereotactic radiosurgery 7 days before and whole brain radiotherapy 21 days before their first dose of study drug.
-
Investigational therapy administered within the 28 days or 5 half lives:
- Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half-lives
- CYP3A strong or moderate inducers: 4 weeks
- Systemic anticancer therapy or investigational therapy 3 weeks or 5 half-lives,
- Immunotherapy with checkpoint inhibitor: 4 weeks
-
Curative-intent radiation therapy ≤ 4 weeks or palliative radiation therapy,
-
Uncontrolled or significant cardiovascular disease:
- QTcF at rest, where the mean QTcF interval is > 480 milliseconds
- Myocardial infarction within 6 months
- Uncontrolled angina pectoris within 6 months
- New York Heart Association Class 3 or 4 congestive heart failure
- Uncontrolled hypertension
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RAIN-32 (Milademetan) RAIN-32 260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle. Trabectedin Trabectedin 1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks.
- Primary Outcome Measures
Name Time Method Compare Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR) Between the Milademetan Treatment Arm and Trabectedin Control Arm from the randomization date to date of documented progression or death, up to 13 months PFS is defined as the time from randomization to the earliest date of the first objective documentation of radiographic disease progression, or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events Until Approximately 30 Days After the Last Study Drug From first dose date to 30 days after the last dose date or the primary study completion date whichever came first; up to 26.6 months. All AEs were collected from the initiation of study treatment until 30 days after the last administration study drug or until initiation of another anticancer therapy, whichever came first; up to 26.6 months.
Overall Survival (OS) From randomization date to death. The result is based on primary analysis data cut. OS as measured from the date of randomization to date of death by any cause
Disease Control Rate (DCR) From the randomization date to first CR, PR or SD >= 16 weeks or the primary study completion date; up to 26.6 months. DCR defined as the percentage of patients who have achieved CR, PR, or SD for \>= 16 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Objective Response Rate (ORR) From randomization date to the first confirmed complete or partial response, or study completion date; up to 26.6 months. ORR defined as the percentage of patients who have achieved a confirmed CR, PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
PFS by Investigator Assessments disease progression or death PFS defined as the time from randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, based on Investigator assessments
Trial Locations
- Locations (71)
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Santo Stefano Hospital - ASL 4 Toscana
🇮🇹Prato, Italy
Institute of Cancer Research and Treatment of Candiolo - IRCCS
🇮🇹Turin, Italy
Duke University School of Medicine, Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Institut Bergonie
🇫🇷Bordeaux, Nouvelle Aquitaine, France
ICANS
🇫🇷Strasbourg, Grand Est, France
Medical University Vienna, Department of Internal Medicine I
🇦🇹Vienna, Austria
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Ghent University, Oncology Center
🇧🇪Ghent, Belgium
University Hospitals Leuven Campus Gasthuisberg
🇧🇪Leuven, Belgium
Institute Claudius Regaud
🇫🇷Toulouse, Occitanie, France
Centre Antoine Lacassagne
🇫🇷Nice, Provence-Alpes-Côte d'Azur, France
CHU La Timone - Oncologie medicale
🇫🇷Marseille, Prvence-Alpes-Cote d'Azu, France
Gustave Roussy
🇫🇷Villejuif, France
Leon Berard Center
🇫🇷Lyon, France
Malkhaz Katsiashvili Multiprofile Emergency Medicin Center LLC
🇬🇪Tbilisi, Georgia
The Christie NHS Foundation Trust, Department of Medical Oncology
🇬🇧Manchester, United Kingdom
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
University Polyclinic Hospital "Paolo Giaccone" Palermo
🇮🇹Palermo, Italy
University General Hospital Gregorio Marañon
🇪🇸Madrid, Spain
LTD Caucasus Medical Centre
🇬🇪Tbilisi, Georgia
M. Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma
🇵🇱Warsaw, Poland
University Hospital Ulm
🇩🇪Ulm, Germany
Severance Hospital, Yonsei University Health System Seoul
🇰🇷Seoul, Korea, Republic of
St Vincent's University Hospital
🇮🇪Dublin, Ireland
University Hospital Campus Bio-Medico
🇮🇹Rome, Italy
National Cancer Institute-IRCCS "Fondazione G. Pascale"
🇮🇹Naples, Italy
Münster University Hospital
🇩🇪Münster, Germany
Passeig de la Vall d'Hebron 119-129
🇪🇸Barcelona, Spain
Asan Medical Center, Department of Oncology
🇰🇷Seoul, Korea, Republic of
The Royal Marsden Hospital NHS Foundation Trust
🇬🇧London, Chelsea, United Kingdom
University Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Helios Hospital Bad Saarow, Clinic for Hematology, Oncology and Palliative Medicine
🇩🇪Bad Saarow, Bradenburg, Germany
University Hospital Foundation Jimenez Diaz
🇪🇸Madrid, Spain
CU Anschutz Medical Campus, Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
UCLA Department of Medicine - Hematology/ Oncology
🇺🇸Santa Monica, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Sarcoma Oncology Research Center, LLC
🇺🇸Santa Monica, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Abramson Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Georges-Francois Leclerc Cancer Research Center
🇫🇷Dijon, Bourgogne-Franche-Comté, France
Centre Hospitalier de Poitiers
🇫🇷Poitiers, Nouvelle Aquitaine, France
LTD High -Tech Hospital MedCenter
🇬🇪Batumi, Georgia
LLC Todua Clinica
🇬🇪Tbilisi, Georgia
LTD Health House
🇬🇪Tbilisi, Georgia
University Medical Center-Mainz
🇩🇪Mainz, Germany
University Hospital Mannheim, Mannheim Cancer Center
🇩🇪Mannheim, Germany
HELIOS Hospital Berlin-Buch
🇩🇪Berlin, Germany
Santo Stefano Hospital of Prato - USL Company Toscana Center
🇮🇹Prato, Italy
National Cancer Institute, IRCCS
🇮🇹Milan, Italy
Veneto Oncology Institute (IOV), IRCCS
🇮🇹Padova, Italy
Department of Clinical Oncology, Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Northwestern Memorial Hospital
🇺🇸Chicago Heights, Illinois, United States
University Hospital Salzburg
🇦🇹Salzburg, Austria
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Order Hospital Linz - Sisters of Mercy
🇦🇹Linz, Austria
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan