Gastric Cancer Clinical Trial
Official title:
A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)
Verified date | August 2023 |
Source | Rain Oncology Inc |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 40 |
Est. completion date | October 15, 2023 |
Est. primary completion date | October 15, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 - Adequate renal function - Creatinine clearance = 30mL/min, as calculated using the modified Cockcroft-Gault equation - 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 presence of liver metastases Exclusion Criteria: - 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 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 |
Country | Name | City | State |
---|---|---|---|
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | University of Cincinnati Medical Center | Cincinnati | Ohio |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Florida Cancer Specialists | Fort Myers | Florida |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
United States | Stanford University Medical Center | Palo Alto | California |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Florida Cancer Specialists | Saint Petersburg | Florida |
United States | Sanford Health | Sioux Falls | South Dakota |
United States | Hematology Oncology Associates of Central NY | Syracuse | New York |
United States | Northwest Medical Specialities | Tacoma | Washington |
Lead Sponsor | Collaborator |
---|---|
Rain Oncology Inc |
United States,
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 criteria | 3 years | ||
Secondary | Duration of Response (DOR) | DOR defined as the time from the date of first documentation of CR or PR according to RECIST v1.1 to the date of disease progression or death due to any cause according to Investigator assessment | 3 years | |
Secondary | Progression-free Survival (PFS) | PFS defined as the time from the date of the first dose of the study drug to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause according to Investigator assessment | 3 years | |
Secondary | Growth Modulation Index (GMI) | GMI defined as the ratio of Time to Progression (TTP) with the nth line of therapy (TTPn; here defined as milademetan) to the most recent prior line of therapy (TTPn-1) | 3 years | |
Secondary | Disease Control Rate (DCR) | DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for = 16 weeks | 3 years | |
Secondary | Overall Survival (OS) | OS as measured from the date of the first dose of the study drug until the date of death due to any cause | 3 years |
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