- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05012397
Milademetan in Advanced/Metastatic Solid Tumors
A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)
Study Overview
Status
Conditions
- Melanoma
- Sarcoma
- Cervical Cancer
- Testicular Germ Cell Tumor
- Gastric Cancer
- Non Small Cell Lung Cancer
- Cholangiocarcinoma
- Lung Adenocarcinoma
- Solid Tumors
- Pancreas Cancer
- Head and Neck Carcinoma
- Biliary Tract Cancer
- Ovarian Carcinoma
- Adrenocortical Carcinoma
- Bladder Urothelial Carcinoma
- Breast Cancer Invasive
- Stomach Adenocarcinoma
- MDM2 Gene Amplification
Intervention / Treatment
Detailed Description
Approximately 65 patients will be enrolled to receive milademetan.
Patients will receive the study drug until reaching unequivocal disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version [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). 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 the study drug, whichever comes first.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Clinical Operations
- Phone Number: 5109535559
- Email: rain3202@rainoncology.com
Study Locations
-
-
California
-
Palo Alto, California, United States, 94305
- Stanford University Medical Center
-
-
Florida
-
Fort Myers, Florida, United States, 33901
- Florida Cancer Specialists
-
Saint Petersburg, Florida, United States, 33705
- Florida Cancer Specialists
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02214
- Massachusetts General Hospital
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
-
Syracuse, New York, United States, 13057
- Hematology Oncology Associates of Central NY
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
Ohio
-
Cincinnati, Ohio, United States, 45267
- University of Cincinnati Medical Center
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57104
- Sanford Health
-
-
Tennessee
-
Nashville, Tennessee, United States, 37203
- Tennessee Oncology, PLLC
-
-
Texas
-
Houston, Texas, United States, 77030
- MD Anderson Cancer Center
-
-
Washington
-
Tacoma, Washington, United States, 77030
- Northwest Medical Specialities
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Milademetan (RAIN-32)
260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: 3 years
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of Response (DOR)
Time Frame: 3 years
|
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
|
Progression-free Survival (PFS)
Time Frame: 3 years
|
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
|
Growth Modulation Index (GMI)
Time Frame: 3 years
|
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
|
Disease Control Rate (DCR)
Time Frame: 3 years
|
DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks
|
3 years
|
Overall Survival (OS)
Time Frame: 3 years
|
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
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Biliary Tract Diseases
- Pancreatic Diseases
- Adrenal Gland Diseases
- Adrenal Cortex Neoplasms
- Adrenal Gland Neoplasms
- Adrenal Cortex Diseases
- Neoplasms
- Carcinoma
- Adenocarcinoma
- Pancreatic Neoplasms
- Cholangiocarcinoma
- Adenocarcinoma of Lung
- Biliary Tract Neoplasms
- Adrenocortical Carcinoma
Other Study ID Numbers
- RAIN-3202
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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