Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma
Advanced Dedifferentiated Liposarcoma, Locally Advanced Dedifferentiated Liposarcoma, Metastatic Dedifferentiated Liposarcoma
About this trial
This is an interventional treatment trial for Advanced Dedifferentiated Liposarcoma
Eligibility Criteria
Inclusion Criteria: ELIGIBILITY CRITERIA (STEP 1): Patients must have histologically documented dedifferentiated liposarcoma (DDLPS). Patients with mixed well-differentiated/dedifferentiated liposarcoma (WD/DD LPS) tumors are eligible provided there is a histologically confirmed DDLPS component at some point during the treatment course Disease must be metastatic or locally advanced and surgically unresectable, in the opinion of the treating investigator Note: Intact retinoblastoma protein (RB) can be assumed in DDLPS. In a query of project Genomics Evidence Neoplasia Information Exchange (GENIE) (American Association for Cancer Research [AACR]), including 286 DDLPS tumors, the rate of RB1 mutation in DDLPS was 1.37%. Therefore, molecular testing to determine intact Rb is not required ELIGIBILITY CRITERIA (STEP 1): Patients must have at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria to be eligible for this study. Previously radiated lesions should not be used as target lesions unless there is documented evidence of disease progression of that lesion after radiation ELIGIBILITY CRITERIA (STEP 1): Patients may have received any number of prior systemic treatment lines for DDLPS, including none ELIGIBILITY CRITERIA (STEP 1): Patients must have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, and with the exceptions of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement ELIGIBILITY CRITERIA (STEP 1): Patients must have completed all prior anti-cancer treatment, including radiation, >= 14 days prior to registration ELIGIBILITY CRITERIA (STEP 1): Age >= 18 years ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 ELIGIBILITY CRITERIA (STEP 1): Absolute neutrophil count (ANC) >= 1000/mm^3 ELIGIBILITY CRITERIA (STEP 1): Platelet count >= 100,000/mm^3 ELIGIBILITY CRITERIA (STEP 1): Hemoglobin >= 9 g/dL ELIGIBILITY CRITERIA (STEP 1): Creatinine clearance (CrCl) >= 30 mL/min ELIGIBILITY CRITERIA (STEP 1): Total bilirubin =< 1.5 x upper limit of normal (ULN) ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN ELIGIBILITY CRITERIA (STEP 1): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible, patients should be class IIB or better. Furthermore, patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction ELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated ELIGIBILITY CRITERIA (STEP 1): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently receiving treatment, they are eligible if they have an undetectable HCV viral load ELIGIBILITY CRITERIA (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial ELIGIBILITY CRITERIA (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients participating on this trial may not be receiving other anti-neoplastic therapies and there should be no anticipated need for such therapy ELIGIBILITY CRITERIA (STEP 1): Patients with treated brain metastases that are non-progressing are eligible if follow-up brain imaging performed at least 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible ELIGIBILITY CRITERIA (STEP 1): Patients must be able to swallow oral medications RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): In order to cross over to Arm 2, patients must meet the same eligibility criteria as described above RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Patients must have demonstrated progression of disease on palbociclib monotherapy (Arm 1) per RECIST version 1.1 criteria Exclusion Criteria: ELIGIBILITY CRITERIA (STEP 1): Patients may not have received prior treatment with CDK4/6 inhibitors (including, but not limited to: palbociclib, ribociclib or abemaciclib) or anti-PD-1/anti-PD-L1 antibodies ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required ELIGIBILITY CRITERIA (STEP 1): Patients must not have an active autoimmune disease with the exception of vitiligo, well-controlled asthma or allergic rhinitis, type 1 diabetes, psoriasis or hypothyroidism. Patients with a history of adrenal insufficiency are eligible if on a stable dose of prednisone =< 10 mg or equivalent ELIGIBILITY CRITERIA (STEP 1): Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any other condition that would limit compliance with study requirements ELIGIBILITY CRITERIA (STEP 1): Patients may not require the use of chronic steroids in excess of 10 mg prednisone daily or equivalent ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to re-registration 2 weeks ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required washout period prior to re-registration is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Patients may not have experienced a grade 3 or higher non-hematologic adverse event deemed clinically significant in the opinion of the treating investigator, or have discontinued palbociclib due to toxicity, while participating on Arm 1 Patients must also have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to Arm 1 treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, and with the exceptions of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement Note: Patients who underwent dose reduction of palbociclib during treatment on Arm 1 will begin treatment on Arm 2 at the same dose (i.e. dose re-escalation is not allowed) RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Patients may not have received prior treatment with anti-PD-1/anti-PD-L1 antibodies RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to re-registration is required
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Cancer Center at Saint Joseph's
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Mission Hope Medical Oncology - Arroyo Grande
- Mercy Cancer Center �� Carmichael
- Mercy San Juan Medical Center
- City of Hope Comprehensive Cancer Center
- Mercy Cancer Center - Elk Grove
- Mercy Cancer Center - Rocklin
- Mercy Cancer Center - Sacramento
- Pacific Central Coast Health Center-San Luis Obispo
- Mission Hope Medical Oncology - Santa Maria
- Woodland Memorial Hospital
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Saint Francis Cancer Center
- Porter Adventist Hospital
- Mercy Medical Center
- Southwest Oncology PC
- Saint Anthony Hospital
- Littleton Adventist Hospital
- Longmont United Hospital
- Parker Adventist Hospital
- Saint Mary Corwin Medical Center
- MedStar Washington Hospital Center
- Mayo Clinic in Florida
- NorthShore University HealthSystem-Evanston Hospital
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Jennie Edmundson Memorial Hospital
- Alegent Health Mercy Hospital
- Heartland Oncology and Hematology LLP
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Hospital
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Saint Joseph Mount Sterling
- Mayo Clinic in Rochester
- Nebraska Medicine-Bellevue
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
- Nebraska Methodist Hospital
- Oncology Associates PC
- Nebraska Medicine-Village Pointe
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Roswell Park Cancer Institute
- UH Seidman Cancer Center at UH Avon Health Center
- UHHS-Chagrin Highlands Medical Center
- Geauga Hospital
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- University Hospitals Parma Medical Center
- UH Seidman Cancer Center at Firelands Regional Medical Center
- UH Seidman Cancer Center at Saint John Medical Center
- University of Oklahoma Health Sciences Center
- Huntsman Cancer Institute/University of Utah
- Virginia Cancer Institute
- VCU Massey Cancer Center at Stony Point
- Virginia Commonwealth University/Massey Cancer Center
- Harrison Medical Center
- Medical College of Wisconsin
- ProHealth D N Greenwald Center
- ProHealth Oconomowoc Memorial Hospital
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (palbociclib)
Arm II (palbociclib, cemiplimab)
Patients receive palbociclib PO on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.
Patients receive palbociclib PO and cemiplimab IV on study. Patients undergo MRI or a CT scan throughout the trial. Patients may also undergo blood sample collection on study.