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Dedifferentiated LiposarcomaPhase 3MANTRANCT04979442

Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma

A Phase 3 study testing RAIN-32 and Trabectedin in people with Dedifferentiated Liposarcoma, run by Rain Oncology Inc at 71 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Dedifferentiated Liposarcoma
What is being tested?
RAIN-32 and Trabectedin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
71 sitesin 15 countries
Study dates
14 Jul 2021to 1 Oct 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

71 sites in 15 countries.

71 sites in 15 countries

United States22 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • CU Anschutz Medical Campus, Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215-5450

  • Northwestern Memorial Hospital

    Chicago Heights, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • The James Cancer Hospital and Solove Research Institute

    Columbus, Ohio, 43210

  • Duke University School of Medicine, Duke Cancer Institute

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stanford Cancer Center

    Palo Alto, California, 94304

  • Abramson Cancer Center at Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19106

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Sarcoma Oncology Research Center, LLC

    Santa Monica, California, 90403

  • UCLA Department of Medicine - Hematology/ Oncology

    Santa Monica, California, 90404

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

France9 sites

  • Institut Bergonie

    Bordeaux, New Aquitaine, 33076

  • Georges-Francois Leclerc Cancer Research Center

    Dijon, Bourgogne-Franche-Comté, 21079

  • Leon Berard Center

    Lyon, 69003

  • CHU La Timone - Oncologie medicale

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

  • Centre Antoine Lacassagne

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

  • Centre Hospitalier de Poitiers

    Poitiers, New Aquitaine, 86021

  • ICANS

    Strasbourg, Grand Est, 67000

  • Institute Claudius Regaud

    Toulouse, Occitanie, 31059

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Italy8 sites

  • National Cancer Institute, IRCCS

    Milan, 20133

  • National Cancer Institute-IRCCS "Fondazione G. Pascale"

    Naples, 80131

  • Veneto Oncology Institute (IOV), IRCCS

    Padova, 35128

  • University Polyclinic Hospital "Paolo Giaccone" Palermo

    Palermo, 90127

  • Santo Stefano Hospital of Prato - USL Company Toscana Center

    Prato, 59100

  • Santo Stefano Hospital - ASL 4 Toscana

    Prato, ASL4

  • University Hospital Campus Bio-Medico

    Rome, 00128

  • Institute of Cancer Research and Treatment of Candiolo - IRCCS

    Turin, 10060

Other trials in Italy

Germany6 sites

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

    Bad Saarow, Bradenburg, 15526

  • HELIOS Hospital Berlin-Buch

    Berlin, 13125

  • University Medical Center-Mainz

    Mainz, 55131

  • University Hospital Mannheim, Mannheim Cancer Center

    Mannheim, 68167

  • Münster University Hospital

    Münster, 48149

  • University Hospital Ulm

    Ulm, 89081

Other trials in Germany

Georgia5 sites

  • LTD High -Tech Hospital MedCenter

    Batumi, 6000

  • LLC Todua Clinica

    Tbilisi, 0112

  • LTD Health House

    Tbilisi, 0144

  • Malkhaz Katsiashvili Multiprofile Emergency Medicin Center LLC

    Tbilisi, 0172

  • LTD Caucasus Medical Centre

    Tbilisi, 0186

Other trials in Georgia

Spain5 sites

  • Passeig de la Vall d'Hebron 119-129

    Barcelona, 08035

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • University General Hospital Gregorio Marañon

    Madrid, 28009

  • University Hospital Foundation Jimenez Diaz

    Madrid, 28040

  • University Hospital Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Austria3 sites

  • Order Hospital Linz - Sisters of Mercy

    Linz, 4010

  • University Hospital Salzburg

    Salzburg, 5020

  • Medical University Vienna, Department of Internal Medicine I

    Vienna, 1090

Other trials in Austria

South Korea3 sites

  • Severance Hospital, Yonsei University Health System Seoul

    Seoul, 03722

  • Asan Medical Center, Department of Oncology

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Belgium2 sites

  • Ghent University, Oncology Center

    Ghent, 9000

  • University Hospitals Leuven Campus Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Taiwan2 sites

  • National Taiwan University Hospital

    Taipei, 100225

  • Taipei Veterans General Hospital

    Taipei, 112

Other trials in Taiwan

United Kingdom2 sites

  • The Royal Marsden Hospital NHS Foundation Trust

    London, Chelsea, SW3 6JJ

  • The Christie NHS Foundation Trust, Department of Medical Oncology

    Manchester, M20 4BX

Other trials in United Kingdom

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

Hong Kong1 site

  • Department of Clinical Oncology, Prince of Wales Hospital

    Hong Kong

Other trials in Hong Kong

Ireland1 site

  • St Vincent's University Hospital

    Dublin, D04 N2E0

Other trials in Ireland

Poland1 site

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

    Warsaw, 02-781

Other trials in Poland

About this study

Official title: A Randomized Multicenter Phase 3 Study of Milademetan Versus Trabectedin in Patients With Dedifferentiated Liposarcoma

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.

Read the 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.

Being tested
RAIN-32, Trabectedin
Keywords
sarcoma, MDM2, pleomorphic liposarcoma
Medical subject headings
Liposarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAIN-32Drug

    Also called Milademetan

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

  • TrabectedinDrug

    Also called Yondelis

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

Study groups in NCT04979442
Study groupRoleWhat they receive
RAIN-32 (Milademetan)Experimental260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle.
Receives: Drug: RAIN-32
TrabectedinActive comparator1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks.
Receives: Drug: Trabectedin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS as measured from the date of randomization to date of death by any cause

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

  2. Disease Control Rate (DCR)

    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.

    Measured: From the randomization date to first CR, PR or SD >= 16 weeks or the primary study completion date; up to 26.6 months.

  3. Objective Response Rate (ORR)

    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.

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

  4. PFS by Investigator Assessments

    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

    Measured: disease progression or death

  5. Number of Participants With Treatment-emergent Adverse Events Until Approximately 30 Days After the Last Study Drug

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2021
  2. Study start14 Jul 2021
  3. Primary completion1 Oct 2023
  4. Study completion1 Oct 2023

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04979442
Sponsor's protocol ID
RAIN-3201
Acronym
MANTRA
Status last verified
Jan 2025
First submitted
6 Jul 2021
Last updated
14 Jan 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RAIN-32 and Trabectedin in people with Dedifferentiated Liposarcoma, run by Rain Oncology Inc at 71 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, France, Italy, Germany, Georgia and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR) Between the Milademetan Treatment Arm and Trabectedin Control Arm (time frame: from the randomization date to date of documented progression or death, up to 13 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04979442.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.

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