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MANTRA: Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma

Sponsor
Rain Therapeutics Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04979442
Collaborator
(none)
160
Enrollment
71
Locations
2
Arms
47.6
Anticipated Duration (Months)
2.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Multicenter Phase 3 Study of Milademetan Versus Trabectedin in Patients With Dedifferentiated Liposarcoma
Actual Study Start Date :
Jul 14, 2021
Anticipated Primary Completion Date :
Jul 1, 2025
Anticipated Study Completion Date :
Jul 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: RAIN-32 (Milademetan)

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

Drug: RAIN-32
260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Other Names:
  • Milademetan

    		•
    Active Comparator: Trabectedin

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

    Drug: Trabectedin
    1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks
    Other Names:
  • Yondelis

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Compare progression-free survival (PFS) as determined by Blinded Independent Central Review (BICR) between the milademetan treatment arm and trabectedin control arm [4 years]

    Secondary Outcome Measures

    1. Overall survival (OS) [4 years]

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

    2. Disease control rate (DCR) [4 years]

      DCR defined as the percentage of patients who have achieved CR, PR, or SD for ≥ 8 weeks

    3. Objective response rate (ORR) [4 years]

      ORR defined as the percentage of patients who achieve a confirmed CR or PR

    4. Duration of response (DOR) [4 years]

      DOR defined as the time from date of first response to date of disease progression or death

    5. PFS by Investigator assessments [4 years]

      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

    6. Number of participants with treatment-emergent adverse events until approximately 30 days after the last study drug [4 years]

    7. Evaluate the patient-reported outcomes by using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (QLQ-C30) [4 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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:

    1. Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half-lives

    2. CYP3A strong or moderate inducers: 4 weeks

    3. Systemic anticancer therapy or investigational therapy 3 weeks or 5 half-lives,

    4. Immunotherapy with checkpoint inhibitor: 4 weeks

    • Curative-intent radiation therapy ≤ 4 weeks or palliative radiation therapy,

    • Uncontrolled or significant cardiovascular disease:

    1. QTcF at rest, where the mean QTcF interval is > 480 milliseconds

    2. Myocardial infarction within 6 months

    3. Uncontrolled angina pectoris within 6 months

    4. New York Heart Association Class 3 or 4 congestive heart failure

    5. Uncontrolled hypertension

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford Cancer Center Palo Alto California United States 94304
    2 Sarcoma Oncology Research Center, LLC Santa Monica California United States 90403
    3 UCLA Department of Medicine - Hematology/ Oncology Santa Monica California United States 90404
    4 CU Anschutz Medical Campus, Anschutz Cancer Pavilion Aurora Colorado United States 80045
    5 Mayo Clinic Florida Jacksonville Florida United States 32224
    6 University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center Miami Florida United States 33136
    7 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612
    8 Northwestern Memorial Hospital Chicago Heights Illinois United States 60611
    9 Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21231
    10 Massachusetts General Hospital Boston Massachusetts United States 02114
    11 Dana Farber Cancer Institute Boston Massachusetts United States 02215-5450
    12 University of Michigan Ann Arbor Michigan United States 48109
    13 Washington University School of Medicine Saint Louis Missouri United States 63110
    14 Columbia University Medical Center New York New York United States 10032
    15 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    16 Duke University School of Medicine, Duke Cancer Institute Durham North Carolina United States 27710
    17 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    18 The James Cancer Hospital and Solove Research Institute Columbus Ohio United States 43210
    19 Oregon Health & Science University Portland Oregon United States 97239
    20 Abramson Cancer Center at Pennsylvania Hospital Philadelphia Pennsylvania United States 19106
    21 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    22 MD Anderson Cancer Center Houston Texas United States 77030
    23 Order Hospital Linz - Sisters of Mercy Linz Austria 4010
    24 University Hospital Salzburg Salzburg Austria 5020
    25 Medical University Vienna, Department of Internal Medicine I Vienna Austria 1090
    26 Ghent University, Oncology Center Ghent Belgium 9000
    27 University Hospitals Leuven Campus Gasthuisberg Leuven Belgium 3000
    28 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 1Z5
    29 Georges-Francois Leclerc Cancer Research Center Dijon Bourgogne-Franche-Comté France 21079
    30 ICANS Strasbourg Grand Est France 67000
    31 Institut Bergonie Bordeaux Nouvelle Aquitaine France 33076
    32 Centre Hospitalier de Poitiers Poitiers Nouvelle Aquitaine France 86021
    33 Institute Claudius Regaud Toulouse Occitanie France 31059
    34 Centre Antoine Lacassagne Nice Provence-Alpes-Côte d'Azur France 06189
    35 CHU La Timone - Oncologie medicale Marseille Prvence-Alpes-Cote d'Azu France 13005
    36 Leon Berard Center Lyon France 69003
    37 Gustave Roussy Villejuif France 94805
    38 LTD High -Tech Hospital MedCenter Batumi Georgia 6000
    39 LLC Todua Clinica Tbilisi Georgia 0112
    40 LTD Health House Tbilisi Georgia 0144
    41 Malkhaz Katsiashvili Multiprofile Emergency Medicin Center LLC Tbilisi Georgia 0172
    42 LTD Caucasus Medical Centre Tbilisi Georgia 0186
    43 Helios Hospital Bad Saarow, Clinic for Hematology, Oncology and Palliative Medicine Bad Saarow Bradenburg Germany 15526
    44 HELIOS Hospital Berlin-Buch Berlin Germany 13125
    45 University Medical Center-Mainz Mainz Germany 55131
    46 University Hospital Mannheim, Mannheim Cancer Center Mannheim Germany 68167
    47 Münster University Hospital Münster Germany 48149
    48 University Hospital Ulm Ulm Germany 89081
    49 Department of Clinical Oncology, Prince of Wales Hospital Hong Kong Hong Kong
    50 St Vincent's University Hospital Dublin Ireland D04 N2E0
    51 National Cancer Institute, IRCCS Milan Italy 20133
    52 National Cancer Institute-IRCCS "Fondazione G. Pascale" Naples Italy 80131
    53 Veneto Oncology Institute (IOV), IRCCS Padova Italy 35128
    54 University Polyclinic Hospital "Paolo Giaccone" Palermo Palermo Italy 90127
    55 Santo Stefano Hospital of Prato - USL Company Toscana Center Prato Italy 59100
    56 Santo Stefano Hospital - ASL 4 Toscana Prato Italy ASL4
    57 University Hospital Campus Bio-Medico Rome Italy 00128
    58 Institute of Cancer Research and Treatment of Candiolo - IRCCS Turin Italy 10060
    59 Severance Hospital, Yonsei University Health System Seoul Seoul Korea, Republic of 03722
    60 Asan Medical Center, Department of Oncology Seoul Korea, Republic of 05505
    61 Samsung Medical Center Seoul Korea, Republic of 06351
    62 M. Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma Warsaw Poland 02-781
    63 Passeig de la Vall d'Hebron 119-129 Barcelona Spain 08035
    64 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08041
    65 University General Hospital Gregorio Marañon Madrid Spain 28009
    66 University Hospital Foundation Jimenez Diaz Madrid Spain 28040
    67 University Hospital Miguel Servet Zaragoza Spain 50009
    68 National Taiwan University Hospital Taipei Taiwan 100225
    69 Taipei Veterans General Hospital Taipei Taiwan 112
    70 The Royal Marsden Hospital NHS Foundation Trust London Chelsea United Kingdom SW3 6JJ
    71 The Christie NHS Foundation Trust, Department of Medical Oncology Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • Rain Therapeutics Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rain Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT04979442
    Other Study ID Numbers:
    • RAIN-3201
    First Posted:
    Jul 28, 2021
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Rain Therapeutics Inc.
    sarcoma
    MDM2
    pleomorphic liposarcoma
    Additional relevant MeSH terms:
    Liposarcoma
    Trabectedin

    Study Results

    No Results Posted as of Aug 5, 2022