Palbociclib and Pembrolizumab in Sarcoma

NCT ID: NCT06113809

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-01
• Study Completion Date: 2028-07-31

Brief Summary

This is a single-arm open-label window of opportunity clinical study assessing the impact of pre-treatment with palbociclib in patients with soft tissue sarcomas for which PD-1 inhibitors are approved (includes undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, or alveolar soft part sarcoma).

Detailed Description

Patients will be given palbociclib for 2 weeks following a pre-treatment ultrasound guided biopsy used to establish immunological baseline of the tumor microenvironment. After 2 weeks of palbociclib therapy, a second 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 may be performed if the subject consents. At 8 weeks of therapy disease response will be assessed as per standard of care.

Conditions

Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

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

Intervention Type: DRUG

Pembrolizumab is a PD-1 blocking antibody.

Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV)

Interventions

Palbociclib

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

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is a PD-1 blocking antibody.

Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients aged > or = 12 years old
• ECOG Performance Status of < or = 2
• Any patient with the diagnosis of locally advanced, unresectable or metastatic sarcoma for which PD-1 inhibitors are approved (undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, alveolar soft part sarcoma) who have progressed on at least 1 prior line of therapy. Prior immunotherapy treatment is allowed, including prior treatment with a PD-1 inhibitor.
• 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 < 18 years old.

Exclusion Criteria

• Lab values in the below ranges:
• Neutrophil count < 1000/mm3
• Platelet count < 100,000/mm3L
• 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 > 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
• 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
• 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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John Rieth

OTHER

Sponsor Role: lead

Responsible Party

John Rieth

Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Rieth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa Hospitals & Clinics

Locations

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

John Rieth, MD

Role: CONTACT

john-rieth@uiowa.edu

3193561616

Facility Contacts

John Rieth, MD

Role: primary

john-rieth@uiowa.edu

319-356-1616

Other Identifiers

202305133

Identifier Type: -

Identifier Source: org_study_id