Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma
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|ClinicalTrials.gov Identifier: NCT04420975|
Recruitment Status : Active, not recruiting
First Posted : June 9, 2020
Last Update Posted : November 21, 2022
|Condition or disease||Intervention/treatment||Phase|
|Leiomyosarcoma Malignant Peripheral Nerve Sheath Tumor Myxofibrosarcoma Pleomorphic Rhabdomyosarcoma Resectable Dedifferentiated Liposarcoma Resectable Soft Tissue Sarcoma Resectable Undifferentiated Pleomorphic Sarcoma Soft Tissue Fibrosarcoma Spindle Cell Sarcoma Stage I Retroperitoneal Sarcoma AJCC (American Joint Committee on Cancer) v8 Stage I Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IA Retroperitoneal Sarcoma AJCC v8 Stage IA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IB Retroperitoneal Sarcoma AJCC v8 Stage IB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage II Retroperitoneal Sarcoma AJCC v8 Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage III Retroperitoneal Sarcoma AJCC v8 Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IIIA Retroperitoneal Sarcoma AJCC v8 Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IIIB Retroperitoneal Sarcoma AJCC v8 Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Storiform-Pleomorphic Malignant Fibrous Histiocytoma Synovial Sarcoma Undifferentiated High Grade Pleomorphic Sarcoma of Bone Undifferentiated Pleomorphic Sarcoma Undifferentiated Pleomorphic Sarcoma With Osteoclast-Like Giant Cells Undifferentiated Pleomorphic Sarcoma, Inflammatory Variant Undifferentiated Spindle Cell Sarcoma||Procedure: Definitive Surgical Resection Biological: Nanoplexed Poly I:C BO-112 Biological: Nivolumab Radiation: Radiation Therapy||Phase 1|
I. To determine the safety and tolerability of integrating BO-112, and BO-112 with nivolumab in soft tissue sarcoma patients undergoing preoperative radiotherapy.
I. Determine the change in T cell infiltration at surgical resection from baseline as measured by immunohistochemistry.
II. Assess treatment effect (necrosis score) of BO-112 and BO-112 in combination with nivolumab in soft tissue sarcoma patients receiving preoperative hypofractionated radiotherapy, compared to patients treated on a recently completed phase 2 study of preoperative hypofractionated radiotherapy alone.
III. Evaluate the 2-year rate of local and distant metastasis of BO-112 and BO-112 in combination with nivolumab in patients with localized resectable soft tissue sarcoma receiving preoperative hypofractionated radiotherapy, as compared to historical patients receiving preoperative radiotherapy alone.
I. Evaluate the dynamics of the intratumoral T cell phenotype. II. Assess the capacity to grow ex vivo tumor infiltrating lymphocytes from patients treated with BO-112 and BO-112 in combination with nivolumab.
III. Analyze changes in T-cell receptor (TCR) repertoire in tumor infiltrating lymphocytes and peripheral blood mononuclear cells (PBMCs) between baseline, post-treatment, and ex vivo cultured tumor infiltrating lymphocyte (TIL) samples.
IV. For patients with disease burden outside of the resected lesion, assess imaging response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Patients receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15 and nivolumab intravenously (IV) over 30-60 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy on days 8-12 for a total of 5 fractions. Patients then undergo standard of care definitive surgical resection on day 26 to 50.
After completion of study treatment, patients are followed up at 2 weeks, 3 months, and between 6-12, 12-18, and 18-24 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Nivolumab and Intratumoral BO 112 for Resectable Soft Tissue Sarcoma|
|Actual Study Start Date :||October 29, 2020|
|Estimated Primary Completion Date :||January 31, 2024|
|Estimated Study Completion Date :||January 31, 2025|
Experimental: Treatment (BO-112, nivolumab)
Patients receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15 and nivolumab IV over 30-60 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy on days 8-12 for a total of 5 fractions. Patients then undergo standard of care definitive surgical resection on day 26 to 50.
Procedure: Definitive Surgical Resection
Undergo definitive surgical resection
Biological: Nanoplexed Poly I:C BO-112
Radiation: Radiation Therapy
Undergo radiation therapy
- Incidence of adverse events (AEs) [ Time Frame: study enrollment through 100 days after the last dose of study drug ]AEs will be tabulated by type, severity, and the proportion of subject experiencing the event.
- Immune-oncologic impact of the BO-112 or the combined regimen of nivolumab and BO-112 [ Time Frame: from the date of study drug initiation until 50 days after study drug initiation (or the date of surgery, whichever comes first) ]Statistical analysis of immune-oncologic changes will be performed by comparing results from surgical specimens with baseline biopsy specimens. For immunohistochemical parameters, the percentage of CD4+ (cluster of differentiation 4) or CD8+((cluster of differentiation 8) cells will be compared between biopsy and surgical specimens using a paired two-tailed ratio T-test comparing means.
- Pathologic treatment effect [ Time Frame: At time of surgery ]Will be compared to historical samples receiving preoperative radiotherapy alone. Will use a two-sample paired T-test comparing means.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04420975
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Vishruth Reddy, MD, PhD||UCLA / Jonsson Comprehensive Cancer Center|