Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma

NCT04979442 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: RAIN-3201
• Study Type: interventional
• Target: 175
• Locations: 15 countries
• Sites: 71

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.

Conditions

Dedifferentiated Liposarcoma

Keywords

sarcoma; MDM2; pleomorphic liposarcoma

Outcome Measures

Primary Outcomes (1)

• Compare Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR) Between the Milademetan Treatment Arm and Trabectedin Control Arm

  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.

  from the randomization date to date of documented progression or death, up to 13 months

Secondary Outcomes (5)

• Overall Survival (OS)

  From randomization date to death. The result is based on primary analysis data cut.

• 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.

• Objective Response Rate (ORR)

  From randomization date to the first confirmed complete or partial response, or study completion date; up to 26.6 months.

• PFS by Investigator Assessments

  disease progression or death

• 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.

Study Arms (2)

RAIN-32 (Milademetan)

EXPERIMENTAL

260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle.

Drug: RAIN-32

Trabectedin

ACTIVE COMPARATOR

1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks.

Drug: Trabectedin

Interventions

RAIN-32 DRUG

260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

Also known as: Milademetan

RAIN-32 (Milademetan)

Trabectedin DRUG

1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks

Also known as: Yondelis

Trabectedin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Rain Oncology Inc: lead

Study Sites (71)

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Sarcoma Oncology Research Center, LLC

Santa Monica, California, 90403, United States

Location

UCLA Department of Medicine - Hematology/ Oncology

Santa Monica, California, 90404, United States

Location

CU Anschutz Medical Campus, Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Northwestern Memorial Hospital

Chicago Heights, Illinois, 60611, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5450, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University School of Medicine, Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Abramson Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19106, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Order Hospital Linz - Sisters of Mercy

Linz, 4010, Austria

Location

University Hospital Salzburg

Salzburg, 5020, Austria

Location

Medical University Vienna, Department of Internal Medicine I

Vienna, 1090, Austria

Location

Ghent University, Oncology Center

Ghent, 9000, Belgium

Location

University Hospitals Leuven Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Georges-Francois Leclerc Cancer Research Center

Dijon, Bourgogne-Franche-Comté, 21079, France

Location

ICANS

Strasbourg, Grand Est, 67000, France

Location

Institut Bergonie

Bordeaux, Nouvelle-Aquitaine, 33076, France

Location

Centre Hospitalier de Poitiers

Poitiers, Nouvelle-Aquitaine, 86021, France

Location

Institute Claudius Regaud

Toulouse, Occitanie, 31059, France

Location

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

Location

CHU La Timone - Oncologie medicale

Marseille, Prvence-Alpes-Cote d'Azu, 13005, France

Location

Leon Berard Center

Lyon, 69003, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

LTD High -Tech Hospital MedCenter

Batumi, 6000, Georgia

Location

LLC Todua Clinica

Tbilisi, 0112, Georgia

Location

LTD Health House

Tbilisi, 0144, Georgia

Location

Malkhaz Katsiashvili Multiprofile Emergency Medicin Center LLC

Tbilisi, 0172, Georgia

Location

LTD Caucasus Medical Centre

Tbilisi, 0186, Georgia

Location

Helios Hospital Bad Saarow, Clinic for Hematology, Oncology and Palliative Medicine

Bad Saarow, Bradenburg, 15526, Germany

Location

HELIOS Hospital Berlin-Buch

Berlin, 13125, Germany

Location

University Medical Center-Mainz

Mainz, 55131, Germany

Location

University Hospital Mannheim, Mannheim Cancer Center

Mannheim, 68167, Germany

Location

Münster University Hospital

Münster, 48149, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

Department of Clinical Oncology, Prince of Wales Hospital

Hong Kong, Hong Kong

Location

St Vincent's University Hospital

Dublin, D04 N2E0, Ireland

Location

National Cancer Institute, IRCCS

Milan, 20133, Italy

Location

National Cancer Institute-IRCCS "Fondazione G. Pascale"

Naples, 80131, Italy

Location

Veneto Oncology Institute (IOV), IRCCS

Padua, 35128, Italy

Location

University Polyclinic Hospital "Paolo Giaccone" Palermo

Palermo, 90127, Italy

Location

Santo Stefano Hospital of Prato - USL Company Toscana Center

Prato, 59100, Italy

Location

Santo Stefano Hospital - ASL 4 Toscana

Prato, ASL4, Italy

Location

University Hospital Campus Bio-Medico

Rome, 00128, Italy

Location

Institute of Cancer Research and Treatment of Candiolo - IRCCS

Turin, 10060, Italy

Location

M. Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma

Warsaw, 02-781, Poland

Location

Severance Hospital, Yonsei University Health System Seoul

Seoul, 03722, South Korea

Location

Asan Medical Center, Department of Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Passeig de la Vall d'Hebron 119-129

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

University General Hospital Gregorio Marañon

Madrid, 28009, Spain

Location

University Hospital Foundation Jimenez Diaz

Madrid, 28040, Spain

Location

University Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

National Taiwan University Hospital

Taipei, 100225, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

The Royal Marsden Hospital NHS Foundation Trust

London, Chelsea, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust, Department of Medical Oncology

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Liposarcoma; Sarcoma

Interventions

milademetan; Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Clinical Research
• Organization: Rain Oncology

clinicalresearch@rainoncology.com

7082323791

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 28, 2021
• Study Start: July 14, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Locations

GB (2); PL (1); US (22); HK (1); AU (3); KR (3); IE (1); ES (5); GE (5); TW (2); FR (9); DE (6); CA (1); IT (8); BE (2)