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Milademetan in Advanced/Metastatic Solid Tumors

Sponsor
Rain Therapeutics Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05012397
Collaborator
(none)
65
Enrollment
10
Locations
1
Arm
33
Anticipated Duration (Months)
6.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Nov 1, 2021
Anticipated Primary Completion Date :
Aug 1, 2024
Anticipated Study Completion Date :
Aug 1, 2024

Arms and Interventions

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 Names:
  • Milademetan

    		•

    Outcome Measures

    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 [3 years]

    Secondary Outcome Measures

    1. Duration of Response (DOR) [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) [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) [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) [3 years]

      DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks

    5. Overall Survival (OS) [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford University Medical Center Palo Alto California United States 94305
    2 Florida Cancer Specialists Fort Myers Florida United States 33901
    3 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    4 Massachusetts General Hospital Boston Massachusetts United States 02214
    5 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    6 Washington University School of Medicine Saint Louis Missouri United States 63110
    7 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    8 Duke University Medical Center Durham North Carolina United States 27710
    9 Tennessee Oncology, PLLC Nashville Tennessee United States 37203
    10 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Rain Therapeutics Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rain Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT05012397
    Other Study ID Numbers:
    • RAIN-3202
    First Posted:
    Aug 19, 2021
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Rain Therapeutics Inc.
    MDM2
    Milademetan
    Basket Study
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Aug 17, 2022