- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06113809
Palbociclib and Pembrolizumab in Undifferentiated Pleomorphic Sarcoma (UPS)
Phase Ib Trial Evaluating the Combination of CDK4 Inhibitor With Immunotherapy in Patients With Undifferentiated Pleomorphic Sarcoma (UPS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Mohammed Milhem, MBBS
- Phone Number: (319) 356-2324
- Email: mohammed-milhem@uiowa.edu
Study Locations
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- Recruiting
- University of Iowa Hospitals & Clinics
-
Contact:
- Mohammed Milhem, MBBS
- Phone Number: 319-356-2324
- Email: mohammed-milhem@uiowa.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
A potential subject must meet all the following inclusion criteria to be eligible to participate in the study.
- Male or female patients aged greater than or equal to 12 years old
- ECOG Performance Status of less than or equal to 2
- Any patient with the diagnosis of locally advanced, unresectable or undifferentiated pleomorphic sarcoma (UPS) who have progressed on at least 1 prior line of therapy and for whom pembrolizumab is an appropriate next standard treatment.
- Patients with any number of prior lines of therapy including newly diagnosed locally advanced unresectable or metastatic disease.
- Patients with no known CNS disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing treatment for dexamethasone (as ascertained by clinical examination and brain imaging) during the screening period. Stable dose of anticonvulsants is allowed. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- Ability to understand and the willingness to sign a written informed consent or assent in case of patients less than 18 years old.
Exclusion Criteria:
A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.
Lab values in the below ranges:
- Neutrophil count < 1000/mm3
- Platelet count < 100,000/mm3
- Hemoglobin < 9 g/dL Transfusion to meet eligibility allowed
- AST/SGOT and ALT/SGPT > 3.0x upper limit of normal (ULN) without disease involvement or > 5.0x ULN if the transaminase elevation is due to disease involvement
- Alkaline phosphatase > 5.0x ULN without known bony metastases
- Serum bilirubin > 1.5x ULN
- Serum creatinine > 1.5x ULN or 24-hour creatinine clearance < 30 mL/min per Cockroft- Gault equation
- Total serum calcium < lower limit of normal (LLN) or if calcium is below LLN the corrected calcium for serum albumin is greater than or equal to LLN
- Serum potassium < 3.0
- Serum sodium < 130
- Serum albumin < 2.5 g/dL
- History of myocardial infarction. unstable angina, stroke or transient ischemic attack within 6 months prior to Day 1
- Prior checkpoint inhibitor or CDK4 inhibitor for advanced UPS. If immunotherapy or CDK4 inhibitor was used as part of neoadjuvant therapy, then 6 months should have elapsed from prior immunotherapy or CDK4i use
- History or drug induced pneumonitis (both pembrolizumab and Palbociclib can cause pneumonitis)
- Subjects requiring hemodialysis
- Patients with severe hepatic impairment (Childs-Pugh Class C).
- Other concurrent severe and/or uncontrolled medical conditions in the opinion of the investigator which will preclude participation
- Pregnancy (positive pregnancy test) or lactation
- If you are a woman who can become pregnant, or a man who is sexually active with a partner who can become pregnant you must use two forms of birth control while on the study and for up to 3 months after the last dose of study drug. Patients who have received chemotherapy or any investigational drug < 4 weeks prior to starting study or who have not recovered from side effects of prior therapy (2 weeks of washout)
- Concomitant use of any other anti-cancer therapy or radiation therapy of the target lesion. Palliative radiation therapy is permitted to non-target lesions.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Combination of Palbociclib with Pembrolizumab
Palbociclib given for 2 weeks following a pre-treatment ultrasound guided biopsy used to establish an immunological baseline of the tumor microenvironment.
After the conclusion of palbociclib therapy, a post-treatment biopsy will be performed to assess the impact of palbociclib on the tumor microenvironment; pembrolizumab will be started the same day as the second biopsy.
After 2 doses of pembrolizumab, a third (optional) biopsy could be performed.
|
Palbociclib is a CDK4/6 inhibitor. Palbociclib, 125 mg, (pediatric dose 75mg/m2 up to 125mg) daily for 21 days out of every 28 days, PO (orally) starting 14 days prior to Pembrolizumab Pembrolizumab is a PD-1 blocking antibody. Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV) |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicities (DLTs) and adverse events (AEs) per CTCAE v5
Time Frame: The dose limiting toxicity period is 4 weeks after starting the first dose of pembrolizumab
|
Confirm the safety of the combination of Palbociclib and Pembrolizumab in UPS as defined by the incidence of DLTs
|
The dose limiting toxicity period is 4 weeks after starting the first dose of pembrolizumab
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate per RECIST 1.1 criteria
Time Frame: 8 weeks following treatment intiation
|
To assess the response (per RECIST 1.1 criteria) of patients with advanced UPS with the combination of CDK4/6 inhibitor and anti-PD-1 immunotherapy
|
8 weeks following treatment intiation
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: Up to two years following completion of treatment
|
To assess progression free survival as calculated by the time from start of treatment until the time of progression of disease or death due to any cause
|
Up to two years following completion of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mohammed Milhem, MBBS, University of Iowa Hospitals & Clinics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Connective Tissue
- Neoplasms, Fibrous Tissue
- Histiocytoma
- Sarcoma
- Histiocytoma, Malignant Fibrous
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Immune Checkpoint Inhibitors
- Palbociclib
- Pembrolizumab
Other Study ID Numbers
- 202305133
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Undifferentiated Pleomorphic Sarcoma
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Undifferentiated Pleomorphic Sarcoma | Recurrent Undifferentiated Pleomorphic Sarcoma | Locally Advanced Undifferentiated Pleomorphic Sarcoma | Unresectable Undifferentiated Pleomorphic SarcomaUnited States
-
National Cancer Institute (NCI)SuspendedLocally Advanced Leiomyosarcoma | Metastatic Undifferentiated Pleomorphic Sarcoma | Locally Advanced Liposarcoma | Locally Advanced Undifferentiated Pleomorphic Sarcoma | Locally Advanced Extraskeletal Myxoid Chondrosarcoma | Locally Advanced Unresectable Soft Tissue SarcomaUnited States, Canada
-
Boehringer IngelheimNot yet recruitingAdvanced Soft Tissue Sarcoma | Undifferentiated Pleomorphic Sarcoma (UPS) | Myxofibrosarcoma (MFS)
-
Fred Hutchinson Cancer CenterIncyte CorporationTerminatedRefractory Soft Tissue Sarcoma | Metastatic Leiomyosarcoma | Metastatic Synovial Sarcoma | Metastatic Undifferentiated Pleomorphic Sarcoma | Advanced Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Advanced Synovial Sarcoma | Metastatic Chondrosarcoma | Advanced Leiomyosarcoma | Metastatic Myxoid... and other conditionsUnited States
-
OHSU Knight Cancer InstituteNovartis Pharmaceuticals; Oregon Health and Science UniversityCompletedStage III Soft Tissue Sarcoma AJCC v7 | Stage IV Soft Tissue Sarcoma AJCC v7 | Locally Advanced Leiomyosarcoma | Unresectable Leiomyosarcoma | Myxofibrosarcoma | Metastatic Malignant Peripheral Nerve Sheath Tumor | Metastatic Synovial Sarcoma | Metastatic Undifferentiated Pleomorphic Sarcoma | Unresectable... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingUndifferentiated Pleomorphic Sarcoma | Recurrent Undifferentiated Pleomorphic Sarcoma | Dedifferentiated Liposarcoma | Resectable Dedifferentiated Liposarcoma | Resectable Undifferentiated Pleomorphic Sarcoma | Recurrent Dedifferentiated LiposarcomaUnited States
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight TherapeuticsActive, not recruitingLeiomyosarcoma | Malignant Peripheral Nerve Sheath Tumor | Synovial Sarcoma | Undifferentiated Pleomorphic Sarcoma | Undifferentiated High Grade Pleomorphic Sarcoma of Bone | Myxofibrosarcoma | Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 | Stage III Soft Tissue Sarcoma of the... and other conditionsUnited States
-
Sunshine Guojian Pharmaceutical (Shanghai) Co.,...Not yet recruitingSarcoma, Soft TissueChina
-
Matthew BucknorFocused Ultrasound Foundation; InSightec-TxSonicsRecruitingUndifferentiated Pleomorphic SarcomaUnited States
-
Maria Sklodowska-Curie National Research Institute...UnknownSarcoma | Leiomyosarcoma | Fibrosarcoma | Liposarcoma | Myxoid Liposarcoma | Myosarcoma | Histiocytic Sarcoma | Pleomorphic Liposarcoma | Synovial Sarcoma | Undifferentiated Pleomorphic Sarcoma | Myxofibrosarcoma | Dedifferentiated Liposarcoma | Malignant Peripheral Nerve Sheath Tumors | Malignant Triton Tumor | Pleomorphic... and other conditionsPoland
Clinical Trials on Palbociclib
-
PfizerCompleted
-
PfizerCompleted
-
MegalabsNot yet recruiting
-
PfizerCompletedHealthyUnited States
-
Memorial Sloan Kettering Cancer CenterPfizerCompletedSarcoma | LiposarcomaUnited States
-
PfizerCompleted
-
PfizerCompletedHealthy, Hepatic InsufficiencyUnited States
-
PfizerCompleted