Description:
Randomized, multicenter, open-label, Phase 3 registration study designed to evaluate the
safety and efficacy of milademetan compared to trabectedin in patients with unresectable
(i.e., where resection is deemed to cause unacceptable morbidity or mortality) or metastatic
DD liposarcoma that progressed on 1 or more prior systemic therapies, including at least 1
anthracycline-based therapy.
Title
- Brief Title: Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma
- Official Title: A Randomized Multicenter Phase 3 Study of Milademetan Versus Trabectedin in Patients With Dedifferentiated Liposarcoma
Clinical Trial IDs
- ORG STUDY ID:
RAIN-3201
- NCT ID:
NCT04979442
Conditions
- Dedifferentiated Liposarcoma
Interventions
Drug | Synonyms | Arms |
---|
RAIN-32 | Milademetan | RAIN-32 (Milademetan) |
Trabectedin | Yondelis | Trabectedin |
Purpose
Randomized, multicenter, open-label, Phase 3 registration study designed to evaluate the
safety and efficacy of milademetan compared to trabectedin in patients with unresectable
(i.e., where resection is deemed to cause unacceptable morbidity or mortality) or metastatic
DD liposarcoma that progressed on 1 or more prior systemic therapies, including at least 1
anthracycline-based therapy.
Detailed Description
Approximately 160 patients will be randomly assigned in a 1:1 ratio to receive milademetan or
trabectedin. Randomization will be stratified by the ECOG performance status (0 or 1) and
number of prior treatments (≤ 2 or > 2) for the patient's liposarcoma.
Patients will receive study drug (i.e., milademetan or trabectedin) until reaching
unequivocal disease progression (RECIST 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) and subsequent treatment information (i.e.,
date/duration of treatment, response, and subsequent disease progression). 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 study drug, whichever comes
first.
Trial Arms
Name | Type | Description | Interventions |
---|
RAIN-32 (Milademetan) | Experimental | 260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle. | |
Trabectedin | Active Comparator | 1.5 mg/m2 body surface area as a 24-hour IV infusion, every 3 weeks. | |
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed DD liposarcoma, with or without a WD component (WD/DD
liposarcoma). Note: Patient must be willing to provide an archival tumor tissue sample
that is ≤ 3 years old and of adequate quality or willing to provide a fresh
pretreatment biopsy sample
- Advanced unresectable (i.e., where resection is deemed to cause unacceptable morbidity
or mortality) and/or metastatic WD/DD liposarcoma
- Measurable tumor lesion(s) in accordance with RECIST version 1.1
- Received 1 or more systemic cancer therapy regimens, including at least 1
anthracycline-based regimen, and had radiographic progressive disease (per RECIST
version 1.1) within 6 months before the Screening Visit
- Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery,
radiotherapy, or hormonal therapy
- 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 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 any mouse double minute 2 (MDM2) inhibitor or trabectedin
- Other primary malignancies that have required systemic antineoplastic treatment within
the previous 2 years, except for localized cancers that have apparently been cured
- Gastrointestinal conditions that could affect the absorption of milademetan, in the
opinion of the Investigator
- Uncontrolled infection within the last 7 days requiring IV antibiotics, antivirals, or
antifungals
- Known HIV infection or active Hepatitis B or C
- Untreated brain metastases. Note: Patients who require steroids for brain metastases
must be on a stable or tapering dose of corticosteroids for at least 2 weeks before
randomization. If applicable, patients must complete stereotactic radiosurgery 7 days
before and whole brain radiotherapy 21 days before their first dose of study drug.
- Investigational therapy administered within the 28 days or 5 half lives:
1. Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half-lives
2. CYP3A strong or moderate inducers: 4 weeks
3. Systemic anticancer therapy or investigational therapy 3 weeks or 5 half-lives,
4. Immunotherapy with checkpoint inhibitor: 4 weeks
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Compare progression-free survival (PFS) as determined by Blinded Independent Central Review (BICR) between the milademetan treatment arm and trabectedin control arm |
Time Frame: | 4 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall survival (OS) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | OS as measured from the date of randomization to date of death by any cause |
Measure: | Disease control rate (DCR) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | DCR defined as the percentage of patients who have achieved CR, PR, or SD for ≥ 8 weeks |
Measure: | Objective response rate (ORR) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | ORR defined as the percentage of patients who achieve a confirmed CR or PR |
Measure: | Duration of response (DOR) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | DOR defined as the time from date of first response to date of disease progression or death |
Measure: | PFS by Investigator assessments |
Time Frame: | 4 years |
Safety Issue: | |
Description: | PFS defined as the time from randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, based on Investigator assessments |
Measure: | Number of participants with treatment-emergent adverse events until approximately 30 days after the last study drug |
Time Frame: | 4 years |
Safety Issue: | |
Description: | |
Measure: | Evaluate the patient-reported outcomes by using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (QLQ-C30) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Rain Therapeutics Inc. |
Trial Keywords
- sarcoma
- MDM2
- pleomorphic liposarcoma
Last Updated
August 27, 2021