Clinical trial NCT02301039: SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas
Official title: SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Bone Sarcoma
Lead sponsor: Sarcoma Alliance for Research through Collaboration
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-11-25
Enrollment: 144
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy of pembrolizumab in patients with advanced sarcomas.

Detailed description: This is a multi-institutional phase II study of pembrolizumab in patients with advanced sarcomas. This study will have two treatment groups, one group for patients with soft tissue sarcoma and one group for patients with bone sarcoma.

Initial enrollment for this study included a total of 86 patients with soft tissue sarcoma and bone sarcomas.

In the expansion portion, there will be an additional 30 patients with undifferentiated pleomorphic sarcoma (UPS) and 30 patients with dedifferentiated or other high grade liposarcoma (LPS) enrolled into the study.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years (Age ≥ 12 years for patients with bone sarcomas).
* Histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic high grade soft-tissue or bone sarcoma of one of the following subtypes: soft tissue sarcomas (leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma/MFH and synovial sarcoma), and bone sarcomas (Ewing sarcoma, osteosarcoma, and chondrosarcoma \[de-differentiated or mesenchymal\]).
* ECOG Performance Status of 0 or 1.
* At least one site of measurable disease on CT/MRI scans as defined by RECIST 1.1. Baseline imaging must be performed within 30 days of dosing.
* At least one site of accessible disease for pre- and post-treatment core biopsies for at least 20 patients per arm on the expansion cohorts.
* Patients may have received 1-3 prior systemic therapies in the metastatic setting.
* Adequate organ function within 14 days of dosing
* Must be willing to provide and have available archival tissue for PD-L1 testing.
* Written, voluntary informed consent.
* Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 120 days after last study drug administration. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study.
* Effective methods of birth control include: surgically sterile, barrier device (condom, diaphragm), contraceptive coil, intrauterine device (IUD), and abstinence.
* Life expectancy of \>12 weeks.
* Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression for at least 4 weeks prior to screening, have no evidence of new or enlarging brain metastases, and are off steroids for at least 7 days before first dose of pembrolizumab.

Exclusion Criteria:

* Prior systemic therapy targeting PD-1: PD-L1 axis.
* Patients who are curable by conventional multidisciplinary management.
* Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
* Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation \< 2 weeks prior to screening or who have not recovered adequately from side effects of such therapy.
* Patients who have active infections requiring therapy.
* Patients that are known to be positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive), or Hepatitis C (HCV RNA \[qualitative\] is detected); patients with negative Hepatitis C antibody testing may not need RNA testing.
* Patients that have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
* Patients who received systemic anti-cancer treatment prior to the first dose of study drug within the following time frames:
* Patients with active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with hypothyroidism not from autoimmune disease that is stable on hormone replacement will not be excluded from the study.
* Women who are pregnant or nursing/breastfeeding.
* Known hypersensitivity to pembrolizumab or another mAb.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible.
* Inability to comply with protocol required procedures.
* Patients with medical conditions that require chronic systemic corticosteroid therapy or require any other form of immunosuppressive medication. However, patients using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study: up to 20 mg hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg prednisone) in the evening.
* Patients with the risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).
* Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Assessments will be conducted at 8 weeks, up to 5 years
Secondary outcomes:
measure: Adverse Events Related to Pembrolizumab Treatment in Patients With Advanced Sarcoma, by Patient
timeFrame: Up to 5 years
measure: The Progression-free Survival (PFS)
timeFrame: up to 5 yrs
measure: Response Rate by Immune-related Response Criteria (Ir-RC)
timeFrame: Assessment at 8 weeks, up to 5 years
measure: Overall Survival (OS)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Washington
country: United States
facility: Medstar Health Research Institute
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: The University of Texas MD Anderson Cancer Center
name: Hussein Tawbi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D'Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba II, Baker LH, Maki RG, Reinke D, Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Nov;18(11):1493-1501. doi: 10.1016/S1470-2045(17)30624-1. Epub 2017 Oct 4.