Brief Summary

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with sarcoma that has spread from the primary site to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with metastatic or unresectable sarcoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

164

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Aug 2015

Longer than P75 for phase_2

Geographic Reach

1 country

651 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.6 years study duration

First Submitted

Initial submission to the registry

July 15, 2015

Completed

2 days until next milestone

First Posted

Study publicly available on registry

July 17, 2015

Completed

27 days until next milestone

Study Start

First participant enrolled

August 13, 2015

Completed

3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2019

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

June 16, 2020

Completed

2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2023

Completed

Last Updated

October 17, 2023

Status Verified

September 1, 2023

Enrollment Period

3.6 years

First QC Date

July 15, 2015

Results QC Date

May 20, 2020

Last Update Submit

September 22, 2023

Outcome Measures

Primary Outcomes (1)

Number of Participants Who Achieved a Confirmed Response
The number of participants who achieved a confirmed response is defined as the number of patients having a best objective tumor status of complete response (CR) or partial response (PR) lasting at least 4 weeks as determined using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).
Up to 44 months

Secondary Outcomes (7)

Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Regardless of Attribution
Up to 4 weeks after completion of study treatment
Duration of Response
Time from first response to progression, assessed up to 3 years
6-Month Clinical Benefit Rate [Initial Cohort]
At 6 months
6-Month Clinical Benefit Rate [Expansion LPS and UPS/MFH Cohorts Only]
At 6 months
6-Month Clinical Benefit Rate [Expansion GIST Cohort Only]
At 6 months
+2 more secondary outcomes

Other Outcomes (7)

PD-L1 Expression Assessed Using Immunohistochemistry (IHC)
Up to 3 years
Change in Selected Biomarkers Measured in Serial Peripheral Blood
Baseline to up to 3 years
Selected Biomarkers Measured in Tumor Tissue
Up to week 6
+4 more other outcomes

Study Arms (2)

Arm I (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to Arm II.

Other: Laboratory Biomarker AnalysisBiological: NivolumabOther: Quality-of-Life Assessment

Arm II (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.

Biological: IpilimumabOther: Laboratory Biomarker AnalysisBiological: NivolumabOther: Quality-of-Life Assessment

Interventions

IpilimumabBIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm II (nivolumab, ipilimumab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (nivolumab)Arm II (nivolumab, ipilimumab)

NivolumabBIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Arm I (nivolumab)Arm II (nivolumab, ipilimumab)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (nivolumab)Arm II (nivolumab, ipilimumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

PRE-REGISTRATION ELIGIBILITY CRITERIA:
Patients must have a formalin-fixed, paraffin-embedded (FFPE) tumor block OR 1 representative hematoxylin and eosin (H\&E) and 20 unstained sarcoma tissue slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility
REGISTRATION ELIGIBILITY CRITERIA:
Patients must have histologically confirmed bone or soft tissue sarcoma by central pathology review
Patients must have histologically confirmed liposarcoma (LPS) (only dedifferentiated and pleomorphic; well differentiated not eligible), undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH), or gastrointestinal stromal tumor (GIST)
Measurable disease
Locally advanced/unresectable or metastatic disease
\>= 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy
No prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation =\< 28 days before study registration; no treatment with nitrosourea or mitomycin =\< 42 days before study registration; for GIST, tyrosine kinase inhibitor can be continued for up to 3 days prior to initiation of study treatment
Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 4.0, grade 1 or less
No history of the following:
Active known or suspected autoimmune disease
Patients with human immunodeficiency virus (HIV) are eligible if the lymphocytes \> 350 cluster of differentiation (CD)4+ cells and no detectable viral load
Symptomatic, untreated, or uncontrolled brain metastases present
+41 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (651)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC