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Trial record 1 of 1 for:    NCT05012397
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Milademetan in Advanced/Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT05012397
Recruitment Status : Recruiting
First Posted : August 19, 2021
Last Update Posted : November 15, 2022
Information provided by (Responsible Party):
Rain Therapeutics Inc.

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) ≥ 12 using prespecified biomarker criteria.

Condition or disease Intervention/treatment Phase
Solid Tumors Head and Neck Carcinoma Cholangiocarcinoma Sarcoma Lung Adenocarcinoma Bladder Urothelial Carcinoma Stomach Adenocarcinoma Breast Cancer Invasive Ovarian Carcinoma Cervical Cancer Non Small Cell Lung Cancer Gastric Cancer Biliary Tract Cancer Melanoma Pancreas Cancer MDM2 Gene Amplification Testicular Germ Cell Tumor Adrenocortical Carcinoma Drug: RAIN-32 Phase 2

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 8 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors
Actual Study Start Date : November 1, 2021
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024

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
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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

  2. 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. 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)

  4. 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

  5. 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

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

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 testing, defined as ≥ 12 copies by central diagnostic laboratory or ≥ 12 copies or 6-fold increase by local testing modalities
  • 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 setting of Gilbert's disease

Exclusion Criteria:

  • Prior treatment with a mouse double minute 2 (MDM2) inhibitor
  • Well-differentiated/dedifferentiated liposarcoma or intimal sarcoma
  • Primary malignancies that required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured
  • Primary brain tumor (e.g., glioma)
  • 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

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): NCT05012397

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Contact: Clinical Operations 5109535559 rain3202@rainthera.com

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United States, California
Stanford University Medical Center Recruiting
Palo Alto, California, United States, 94305
United States, Florida
Florida Cancer Specialists Recruiting
Fort Myers, Florida, United States, 33901
Florida Cancer Specialists Recruiting
Saint Petersburg, Florida, United States, 33705
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Rain Therapeutics Inc.
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Responsible Party: Rain Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT05012397    
Other Study ID Numbers: RAIN-3202
First Posted: August 19, 2021    Key Record Dates
Last Update Posted: November 15, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.:
Basket Study
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Pancreatic Neoplasms
Adenocarcinoma of Lung
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Biliary Tract Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Adrenal Cortex Diseases
Adrenal Gland Diseases