Dedifferentiated liposarcoma MedDRA version: 20.0 Level: LLT Classification code 10024631 Term: Liposarcoma NOS System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10024633 Term: Liposarcoma stage unspecified System Organ Class: 100000004864
Conditions
Sponsors
Rain Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet all the following criteria: 1. Is a male or female patient = 18 years old 2. Has a signed and dated informed consent form prior to the start of any study-specific qualification procedures 3. Has histologically confirmed WD/DD liposarcoma, by local pathologic review; central pathologic review will also be performed but is not required for inclusion. Note: Patient must be willing to provide either an archival tumor tissue sample that is = 3 years old and of adequate quality or a fresh pretreatment biopsy sample. If a fresh pretreatment biopsy sample is clinically not recommended and the patient is subsequently documented as exempt by the Sponsor, archival material > 3 years may be acceptable after discussion with the Sponsor 4. Has documented advanced unresectable (i.e., where resection is deemed to cause unacceptable morbidity or mortality) and/or metastatic WD/DD liposarcoma 5. Has measurable tumor lesion(s) in accordance with RECIST version 1.1 6. Has 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 7. Has resolution of any clinically relevant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy. Note: AEs from prior therapy must resolve to Grade = 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of peripheral neuropathy, which must resolve to Grade = 2, and alopecia 8. Has an ECOG performance status of 0 or 1 9. Has adequate bone marrow function, defined as: o Platelet count = 100 × 109/L o Hemoglobin = 9.0 g/dL o Absolute neutrophil count = 1.5 × 109/L 10. Has adequate renal function, defined as creatinine clearance = 30 mL/min, as calculated using the modified Cockcroft-Gault equation (or equivalent glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration formula) 11. Has adequate hepatic function, defined as: Alanine aminotransferase and aspartate aminotransferase = 3 × upper limit of normal (ULN) if no liver metastases are present; = 5 × ULN if liver metastases are present o Total bilirubin = 1.5 × ULN. Patients with Gilbert’s disease who have serum bilirubin level = 3 x ULN, may be enrolled 12. Is willing and able to comply with the protocol requirements. 13. Patients requiring anticoagulation medication should be on a stable regimen, defined as at least 4 weeks on the same dose 14.Patients requiring antihypertensive medication should be on a stable regimen, defined as at least 4 weeks on the same dose 15. If a woman of childbearing potential (WOCBP), must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Cycle 1 Day 1 before receiving her first dose of study drug or within 72 hours of the first dose of study drug Note: A female patient must be willing to use a highly effective contraceptive method as discussed with the Investigator upon randomization through the Treatment Period and until 3 months after the final dose of study drug. A female is considered to be of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months without an alternative medical cause) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) with surgery at least 1 month befor
Exclusion criteria
Exclusion criteria: A patient who meets any of the following criteria will not be eligible to participate in the study: 1-Has received prior treatment with any mouse double minute 2 (MDM2) inhibitor or trabectedin 2. Has other primary malignancies that have required systemic cancers that have apparently been cured (e.g., nonmelanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast) and will not interfere with the study outcomes 3. Has gastrointestinal conditions that could affect the absorption of milademetan, in the opinion of the Investigator 4. Has an uncontrolled infection within the last 7 days requiring IV antibiotics, antivirals, or antifungals 5. Has known HIV infection or active hepatitis B or C infection 6. Has 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. 7. Has not met the minimum washout period before randomization, defined as: a. Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half lives of the inhibitor b. CYP3A strong or moderate inducers (e.g., St. John's wort and modafinil): 4 weeks c. Systemic anticancer therapy (chemotherapy; small molecules, including antibody drug therapy; retinoid therapy; or hormonal therapy) or investigational therapy: 3 weeks or 5 half-lives, whichever is shorter. d. Immunotherapy with checkpoint inhibitor: 4 weeks 8. Has had major surgery = 3 weeks from randomization 9. Has had curative-intent radiation therapy = 4 weeks or palliative radiation therapy, defined as = 30 Gy in = 10 fractions (e.g., 20 Gy in 5 fractions or 8 Gy in 1 fraction) = 2 weeks from randomization 10. Has uncontrolled or significant cardiovascular disease, including: a. QTcF at rest, where the mean QTcF interval is > 480 milliseconds (average of triplicate electrocardiograms [ECGs]) b. Myocardial infarction within 6 months prior to screening c. Uncontrolled angina pectoris within 6 months prior to screening d. New York Heart Association Class 3 or 4 congestive heart failure e. Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) 11. Is a female who is pregnant or breastfeeding or intends to become pregnant during the study 12. Has a concomitant medical condition that would interfere with the assessment of efficacy or increase the risk of toxicity, in the opinion of the Investigator or Sponsor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare progression-free survival (PFS) between the milademetan treatment arm and trabectedin control arm, as determined by blinded independent central review (BICR), in patients with unresectable or metastatic dedifferentiated (DD) liposarcoma, with or without a well-differentiated (WD) component, who progressed on 1 or more prior systemic therapies including at least 1 anthracycline-based therapy.;Secondary Objective: To compare the milademetan treatment arm versus the trabectedin control arm for the following efficacy measures: o Overall survival (OS) o Disease control rate (DCR) by BICR and Investigator assessment o Objective response rate (ORR) by BICR and Investigator assessment o Duration of response (DOR) by BICR and Investigator assessment o PFS by Investigator assessment To assess the safety profile of milademetan To evaluate patient-reported outcomes of quality of life from health economics and outcomes research.;Primary end point(s): The primary efficacy endpoint is Progression Free Survival defined as the time from randomization to the earliest date of the first objective documentation of radiographic disease progression as determined by BICR or death due to any cause. Tumor response will be assessed in accordance with RECIST version 1.1. ;Timepoint(s) of evaluation of this end point: Tumor response evaluations will be performed at screening; at the end of Week 8, Week 16, Week 24, and Week 32; and then every 12 weeks (± 1 week [7 days]) while the patient remains on study drug and any other time during the study as clinically indicated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints include: - Overall Survival (OS) - Disease Control Rate (DSR) by BICR and Investigator assessment - Objective Response Rate (ORR) by BICR and Investigator assessment - Duration Of Response (DOR) by BICR and Investigator assessment - Progression Free Survival (PFS) ;Timepoint(s) of evaluation of this end point: - Overall Survival is measured from the date of randomization to the date of death by any cause. - Disease Control Rate is measured as percentage of patients who have achieved Complete Response, Partial Response, or Stable Disease for = 8 weeks - Objective Response Rate is measured as the percentage of patients who achieve a confirmed Complete Response or Partial Response -Duration Of Response is measured as the time from date of first response to date of disease progression or death - Progression Free Survival is measured as the time from randomization to the earliest date of the first objective documentation of radiographic disease progression, based on Investigator assessments or death due to any cause | — |
Countries
Austria, Belgium, Canada, France, Georgia, Germany, Hong Kong, Ireland, Italy, Korea, Republic of, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial information
Rain Therapeutics Inc.
Outcome results
None listed