Palbociclib and Pembrolizumab in Sarcoma

ConditionSarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12+
SponsorJohn Rieth

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 volunteers

Qualifiers

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

Design model

Single group

Treatments tested in this trial

  • 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

  • Pembrolizumab

    Drug

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

Treatment groups

8 Participants
are divided into 1 treatment group
Group A: Combination of Palbociclib with PembrolizumabExperimental treatment 2 interventions

Trial outcomes

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

Time frame
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

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

Time frame
8 weeks following treatment intiation

Other outcomes

1

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

Time frame
Up to two years following completion of treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

John Rieth

Lead sponsor

University of Iowa

Sponsor institution