Study Stopped
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Milademetan in Advanced/Metastatic Solid Tumors
A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)
1 other identifier
interventional
40
1 country
14
Brief Summary
Phase 2, multicenter, single-arm, open-label basket study designed to evaluate the safety and efficacy of milademetan in patients with advanced or metastatic solid tumors refractory or intolerant to standard-of-care therapy that exhibit wild-type (WT) TP53 and MDM2 copy number (CN) ≥ 8 using prespecified biomarker criteria.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2021
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2021
CompletedFirst Posted
Study publicly available on registry
August 19, 2021
CompletedStudy Start
First participant enrolled
November 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 15, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 15, 2023
CompletedResults Posted
Study results publicly available
October 17, 2024
CompletedOctober 17, 2024
October 1, 2024
2 years
August 13, 2021
August 16, 2024
October 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To Determine the ORR of Treatment With Milademetan in Patients With Advanced/Metastatic Solid Tumors With MDM2 Gene Amplification.
Overall Response Rate (ORR) of treatment with milademetan, as defined as the percentage of patients who have achieved confirmed complete response (CR) or Partial Response (PR) according to RECIST v1.1
From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.
Secondary Outcomes (4)
Duration of Response (DOR)
From start date of response to first PD or study completion date; up to 23.5 months
Progression-free Survival (PFS)
From the first dose date to the earliest date of recurrence, progression, death, or study completion; up to 23.5 months
Growth Modulation Index (GMI)
From the start date of the most recent prior line of therapy to the PD date on the study; up to 23.5 months
Disease Control Rate (DCR)
From first dose date to first CR, PR, or stable disease (SD) >= 16 weeks, or study completion date; up to 23.5 months
Study Arms (1)
Milademetan (RAIN-32)
EXPERIMENTAL260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Interventions
260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Eligibility Criteria
You may qualify if:
- Histologically and/or cytologically confirmed diagnosis of a cancer that is a locally advanced or metastatic solid tumor
- Measurable tumor lesion(s) in accordance with RECIST v1.1
- Received all standard therapy appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard-of-care therapy
- Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
- Presence of WT TP53 and MDM2 gene amplification by tumor tissue/blood testing, defined as ≥ 8 copies in tumor tissue by central laboratory or ≥ 8 copies or 4-fold increase in tumor tissue or blood by local testing
- Prescreening for TP53 and MDM2 at a Central Laboratory:
- MDM2 amplification: CN unknown and where CN cannot be derived for documentation by interpretation of reported results
- MDM2 amplification: CN 6 to 7.9
- MDM2 amplification: 3-3.9-fold increase
- MDM2 amplification with CN ≥ 8 and with equivocal TP53 mutation upon discussion with Sponsor's Medical Monitor
- 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
- +5 more criteria
You may not qualify if:
- Prior treatment with a murine double minute 2 (MDM2) inhibitor
- Well-differentiated/dedifferentiated liposarcoma or intimal sarcoma/cardiac sarcoma
- Primary malignancies that required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured
- Has a primary malignant brain tumor of any grade or histology
- Untreated brain metastases
- Gastrointestinal conditions that could affect the absorption of milademetan, in the opinion of the Investigator
- Known HIV infection or active hepatitis B or C infection
- Major surgery ≤ 3 weeks of the first dose of milademetan
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Stanford University Medical Center
Palo Alto, California, 94305, United States
Florida Cancer Specialists
Fort Myers, Florida, 33901, United States
Florida Cancer Specialists
St. Petersburg, Florida, 33705, United States
Massachusetts General Hospital
Boston, Massachusetts, 02214, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Hematology Oncology Associates of Central NY
Syracuse, New York, 13057, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
Sanford Health
Sioux Falls, South Dakota, 57104, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Northwest Medical Specialities
Tacoma, Washington, 77030, United States
Related Publications (1)
Gounder MM, Bauer TM, Schwartz GK, Weise AM, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru VG, Xu F, Doebele RC, Hong DS. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. J Clin Oncol. 2023 Mar 20;41(9):1714-1724. doi: 10.1200/JCO.22.01285. Epub 2023 Jan 20.
PMID: 36669146BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Research
- Organization
- Rain Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 13, 2021
First Posted
August 19, 2021
Study Start
November 1, 2021
Primary Completion
October 15, 2023
Study Completion
October 15, 2023
Last Updated
October 17, 2024
Results First Posted
October 17, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will not share