About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Single group
Treatments tested in this trial
Palbociclib
DrugPalbociclib 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
DrugPembrolizumab is a PD-1 blocking antibody. Given 14 days following Palbociclib: Pembrolizumab, 200 mg, once every three weeks, intravenously (IV)
Treatment groups
Trial outcomes
Primary outcomes
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
Secondary outcomes
Response rate per RECIST 1.1 criteria
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
Other outcomes
Progression free survival
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
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
John Rieth
Lead sponsor
University of Iowa
Sponsor institution