Palbociclib and Pembrolizumab in Sarcoma

NCT06113809 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202305133
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLTs) and adverse events (AEs) per CTCAE v5

  Confirm the safety of the combination of Palbociclib and pembrolizumab in sarcomas for which PD-1 inhibitors are approved as defined by the incidence of DLTs

  The dose limiting toxicity period is 4 weeks after starting the first dose of pembrolizumab

Secondary Outcomes (1)

• Response rate per RECIST 1.1 criteria

  8 weeks following treatment intiation

Other Outcomes (1)

• Progression free survival

  Up to two years following completion of treatment

Study Arms (1)

Combination of Palbociclib with Pembrolizumab

EXPERIMENTAL

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.

Drug: Palbociclib; Drug: Pembrolizumab

Interventions

Palbociclib 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

Combination of Palbociclib with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is a PD-1 blocking antibody. Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV)

Combination of Palbociclib with Pembrolizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John Rieth: lead

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

palbociclib; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• John Rieth, MD

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Rieth, MD

CONTACT

3193561616; john-rieth@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Model Details: This is a single-arm open-label window of opportunity clinical study assessing the impact of pre-treatment with palbociclib

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: November 2, 2023
• Study Start: February 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)