Sarcoma
Conditions
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.
Interventions
DRUGPalbociclib
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
DRUGPembrolizumab
Pembrolizumab is a PD-1 blocking antibody. Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV)
Sponsors
John Rieth
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-arm open-label window of opportunity clinical study assessing the impact of pre-treatment with palbociclib
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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 \> 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
A potential subject who meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicities (DLTs) and adverse events (AEs) per CTCAE v5 | 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 sarcomas for which PD-1 inhibitors are approved as defined by the incidence of DLTs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate per RECIST 1.1 criteria | 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 |
Countries
United States
Contacts
CONTACTJohn Rieth, MD
PRINCIPAL_INVESTIGATORJohn Rieth, MD
University of Iowa Hospitals & Clinics
Outcome results
None listed