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Solid TumorsPhase 2NCT05012397

Milademetan in Advanced/Metastatic Solid Tumors

A Phase 2 study testing RAIN-32 in people with Solid Tumors and Head and Neck Carcinoma, run by Rain Oncology Inc at 14 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RAIN-32
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
14 sitesUnited States
Study dates
1 Nov 2021to 15 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stanford University Medical Center

    Palo Alto, California, 94305

  • Sanford Health

    Sioux Falls, South Dakota, 57104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Florida Cancer Specialists

    St. Petersburg, Florida, 33705

  • Hematology Oncology Associates of Central NY

    Syracuse, New York, 13057

  • Northwest Medical Specialities

    Tacoma, Washington, 77030

Other trials in United States

About this study

Official title: A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)

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.

Read the 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.

Being tested
RAIN-32
Keywords
MDM2, Milademetan, Basket Study
Medical subject headings
Cholangiocarcinoma, Sarcoma, Adenocarcinoma of Lung, Ovarian Neoplasms, Uterine Cervical Neoplasms, Carcinoma, Non-Small-Cell Lung, Stomach Neoplasms, Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAIN-32Drug

    Also called Milademetan

    260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

Study groups in NCT05012397
Study groupRoleWhat they receive
Milademetan (RAIN-32)Experimental260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Receives: Drug: RAIN-32

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.

Secondary outcomes (4)

  1. 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

    Measured: From start date of response to first PD or study completion date; up to 23.5 months

  2. 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

    Measured: From the first dose date to the earliest date of recurrence, progression, death, or study completion; up to 23.5 months

  3. 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)

    Measured: From the start date of the most recent prior line of therapy to the PD date on the study; up to 23.5 months

  4. Disease Control Rate (DCR)

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

    Measured: From first dose date to first CR, PR, or stable disease (SD) >= 16 weeks, or study completion date; up to 23.5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2021
  2. Study start1 Nov 2021
  3. Primary completion15 Oct 2023
  4. Study completion15 Oct 2023

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05012397
Sponsor's protocol ID
RAIN-3202
Status last verified
Oct 2024
First submitted
13 Aug 2021
Last updated
17 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36669146

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RAIN-32 in people with Solid Tumors and Head and Neck Carcinoma, run by Rain Oncology Inc at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To Determine the ORR of Treatment With Milademetan in Patients With Advanced/Metastatic Solid Tumors With MDM2 Gene Amplification. (time frame: From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05012397, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2024.

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