Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma

  • STATUS
    Recruiting
  • End date
    Jan 31, 2025
  • participants needed
    25
  • sponsor
    Jonsson Comprehensive Cancer Center
Updated on 28 June 2021
platelet count
cancer
monoclonal antibodies
neutrophil count
tumor cells
fibrosarcoma
soft tissue sarcoma
liposarcoma
synovial sarcoma
undifferentiated pleomorphic sarcoma
leiomyosarcoma
sarcoma of the extremity

Summary

This phase I trial studies the side effects of BO-112 when given together with nivolumab before surgery in treating patients with soft tissue sarcoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab and BO-112 before surgery may work better in treating patients with soft tissue sarcoma compared to nivolumab alone.

Description

PRIMARY OBJECTIVE:

I. To explore the safety of BO-112 in combination with nivolumab in soft tissue sarcoma patients undergoing preoperative radiotherapy, as assessed by the frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 toxicity criteria.

SECONDARY OBJECTIVES:

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 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 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.

EXPLORATORY OBJECTIVES:

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 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.

OUTLINE

Patients receive BO-112 intratumorally on days 1, 8, and 15 and nivolumab intravenously (IV) over 30-60 minutes on days 8 and 22 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.

Details
Condition Undifferentiated Pleomorphic Sarcoma With Osteoclast-Like Giant Cells, All Solid Tumors, synovial sarcoma, Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8, leiomyosarcoma, Stage IB Retroperitoneal Sarcoma AJCC v8, Undifferentiated Pleomorphic Sarcoma, Inflammatory Variant, Stage IA Retroperitoneal Sarcoma AJCC v8, Stage IB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8, Stage IA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8, Sarcoma (Pediatric), Solid Tumors, Resectable Undifferentiated Pleomorphic Sarcoma, Stage II Retroperitoneal Sarcoma AJCC v8, Stage I Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8, Soft Tissue Sarcoma, Resectable Soft Tissue Sarcoma, Soft Tissue Fibrosarcoma, Sarcoma, Resectable Dedifferentiated Liposarcoma, Stage I Retroperitoneal Sarcoma American Joint Committee on Cancer (AJCC) v8, Connective and Soft Tissue Neoplasm, Myxofibrosarcoma, Malignant Fibrous Histiocytoma
Treatment radiation therapy, Nivolumab, Definitive Surgical Resection, Immunotherapeutic Agent
Clinical Study IdentifierNCT04420975
SponsorJonsson Comprehensive Cancer Center
Last Modified on28 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent, and assent where appropriate, must be obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Resectable, biopsy proven soft tissue sarcoma of the extremity, trunk or retroperitoneum including undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, dedifferentiated liposarcoma, and synovial sarcoma. Undifferentiated pleomorphic sarcoma encompasses any of the following histologies
Pleomorphic undifferentiated sarcoma
Unclassified spindle cell sarcoma
Spindle cell sarcoma not otherwise specified
Pleomorphic spindle cell sarcoma
Pleomorphic fibroblastic sarcoma
Undifferentiated high-grade pleomorphic sarcoma
Pleomorphic sarcoma with prominent inflammation
Pleomorphic sarcoma with giant cells
Malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes)
Fibrosarcoma
Tumor that is injectable
Hemoglobin >= 9 g/dL
Absolute neutrophil count >= 1,000/mm^3
Platelet count >= 100,000/mm^3 and transfusion independent
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN)
Bilirubin =< 1.5 x ULN; for subjects with documented/suspected Gilbert's disease, bilirubin =< 3 x ULN
Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal unless the patient is on anticoagulant therapy within 28 days prior to enrollment (if the patient is receiving anticoagulant therapy, PT, and a PTT must be within therapeutic range of intended use of anticoagulants)
Patients must be willing to submit blood and tissue specimens for translational medicine studies
Patients must be offered the opportunity to participate in specimen banking for future research
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug
Women must not be breastfeeding
Women of childbearing potential (WOCBP) must be willing to use either two adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from heterosexual activity (complete abstinence) throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include intrauterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, female condoms with spermicide, or oral contraceptives. Spermicides alone are not an acceptable method of contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to highly effective contraception during active participation in study treatment and for a period of 7 months after the last dose of nivolumab
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to use one of the highly effective methods of contraception listed below. Male subjects must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Contraception methods are as follows
Progestogen only hormonal contraception associated with inhibition of ovulation
Hormonal methods of contraception including oral contraceptive pills containing combined estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena
Nonhormonal IUDs, such as ParaGard
Bilateral tubal occlusion
Vasectomized partner with documented azoospermia 90 days after procedure
Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success
Intrauterine hormone-releasing system (IUS)
Complete abstinence
Complete abstinence is defined as the complete avoidance of heterosexual intercourse
Complete abstinence is an acceptable form of contraception for all study drugs and must be used throughout the duration of the study treatment (plus 5 half-lives of the investigational drug plus 30 days)
It is not necessary to use any other method of contraception when complete abstinence is elected
Subjects who choose complete abstinence must continue to have pregnancy tests, as specified
Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject
LESS EFFECTIVE METHODS OF CONTRACEPTION
Diaphragm with spermicide
Cervical cap with spermicide
Vaginal sponge with spermicide
Male or female condom with or without spermicide
A male and a female condom must not be used together
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
UNACCEPTABLE METHODS OF CONTRACEPTION
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal (coitus interruptus)
Spermicide only
Lactation amenorrhea method (LAM)

Exclusion Criteria

Contraindications to tumor biopsy and injections (coagulopathy, known history of keloid formation, etc.)
Women who are pregnant or breastfeeding
Inability to give informed consent
History of other malignancy that can interfere with interpretation of the results
Prior irradiation in the area to be treated with preoperative radiation
Any condition that might interfere with the subject's participation in the study, safety, or in the evaluation of the study results
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
Prior exposure to any Programmed death-ligand 1 (anti-PD-1 or anti-PD-L1 antibody), or any Cytotoxic T lymphocyte-associated antigen (anti-CTLA 4) antibodies
Patients must not have received any live vaccine within 30 days prior to registration. Seasonal flu vaccines and other vaccines that do not contain live virus are permitted
Any concurrent chemotherapy, immunotherapy, or biologic therapy for cancer treatment. Concurrent use of hormones is acceptable
Patient must not have evidence of any clinically significant immunosuppression such as the following: primary immunodeficiency state such as severe combined immunodeficiency disease; concurrent opportunistic infection; receiving systemic immunosuppressive therapy within 28 days before enrollment with the exceptions of intranasal, topical, and inhaled corticosteroids or oral corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
Active or prior documented autoimmune disease within the past 3 years
NOTE: Subjects with active, known or suspected autoimmune disease such as vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Active or prior documented inflammatory bowel disease
History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Exposure to any investigational drug within 7 days prior to screening visit or for which 5 half-lives have not elapsed
Prisoners or subjects who are involuntarily incarcerated
Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
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