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Trial record 1 of 1 for:    RAIN-3201
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Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma (MANTRA)

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ClinicalTrials.gov Identifier: NCT04979442
Recruitment Status : Recruiting
First Posted : July 28, 2021
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
Rain Therapeutics 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.

Condition or disease Intervention/treatment Phase
Dedifferentiated Liposarcoma Drug: RAIN-32 Drug: Trabectedin 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 14, 2021
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Trabectedin

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 Name: 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 Name: Yondelis




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 [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 4 years ]
    OS as measured from the date of randomization to date of death by any cause

  2. Disease control rate (DCR) [ Time Frame: 4 years ]
    DCR defined as the percentage of patients who have achieved CR, PR, or SD for ≥ 8 weeks

  3. Objective response rate (ORR) [ Time Frame: 4 years ]
    ORR defined as the percentage of patients who achieve a confirmed CR or PR

  4. Duration of response (DOR) [ Time Frame: 4 years ]
    DOR defined as the time from date of first response to date of disease progression or death

  5. PFS by Investigator assessments [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 4 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04979442


Contacts
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Contact: Clinical Operations 5109535559 rain3201@rainthera.com

Locations
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United States, California
Sarcoma Oncology Research Center, LLC Recruiting
Santa Monica, California, United States, 90403
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215-5450
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abramson Cancer Center at Pennsylvania Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19106
France
Gustave Roussy Recruiting
Villejuif, France, 94805
Poland
M. Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma Recruiting
Warsaw, Poland, 02-781
Sponsors and Collaborators
Rain Therapeutics Inc.
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Responsible Party: Rain Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04979442    
Other Study ID Numbers: RAIN-3201
First Posted: July 28, 2021    Key Record Dates
Last Update Posted: November 24, 2021
Last Verified: November 2021

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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:
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Liposarcoma
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents