GL-ONC1 with or without Eculizumab in Treating Patients with Solid Organ Cancers before Surgery
This phase Ib trial studies the side effects and best dose of light-emitting oncolytic vaccinia virus GL-ONC1 (GL-ONC1) when given with or without eculizumab in treating patients with solid organ cancers before surgery. A virus called GL-ONC1, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Monoclonal antibodies, such as eculizumab, may interfere with the ability of tumor cells to grow and spread. Giving GL-ONC1 with or without eculizumab may work better in treating patients with solid organ cancers.
- Ability to understand and the willingness to sign a written informed consent
- Histologically-proven diagnosis of advanced (American Joint Committee on Cancer [AJCC], 7th addition: stage III or IV) or aggressive (published disease-specific survival rates less than 20% at 5 years following best currently available therapies) solid organ cancer; this includes but is not limit to: * Metastatic melanoma * Esophageal and gastric adenocarcinoma (stage III/IV) * Cholangiocarcinoma (any stage) * Pancreatic adenocarcinoma (any stage) * Gallbladder cancer (any stage) * Colorectal cancer (stage IV) * High-grade mucinous appendix cancer (any stage) * High-grade gastrointestinal neuroendocrine cancer (any stage) * Mesothelioma (any stage) * High-grade soft tissue sarcoma (any stage)
- Patients must provide written consent to allow a core needle biopsy samples of tumor tissue (primary or metastatic) to be obtained during baseline for analysis of mutations associated with his/her malignancy, and for correlation studies; if available, patients may elect to provide a formalin fixed paraffin embedded (FFPE) tissue block (from his/her primary or metastatic tumor) obtained within 45 days prior to written consent for the clinical trial granting release of the paraffin block; planned to undergo standard surgical resection for potential cure or for palliation when applicable
- Have NO continuing acute toxic effects of any prior therapy, including but not limited to biological therapy, radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) grade =< 1; any other surgery (except biopsies) must have occurred at least 28 days prior to study enrollment
- Have evidence of measurable disease (according to Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Have a life expectancy of at least 3 months
- Absolute neutrophil count (ANC) >= 1.5 x 10^9
- Platelets >= 100 x 10^9 (without platelet transfusion)
- Hemoglobin >= 9.0 g/dL (with or without red blood cell [RBC] transfusion)
- Serum creatinine =< 1.5 x upper limit of normal (ULN)
- Bilirubin =< 1.5 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at =< 2.5 x ULN (in case of liver metastasis AST/ALT at =< 5.0 x ULN)
- Lactate dehydrogenase (LDH) =< 1.5 x ULN
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing
- Have received vaccination against Neisseria meningitidis at least 2 weeks prior to beginning study protocol (only for cohorts where patients receive eculizumab treatment) in accordance with the most current Advisory Committee on Immunization Practices (ACIP) recommendations
- Have negative test result for human immunodeficiency virus (HIV) and hepatitis B or C testing
- Have baseline anti-vaccinia antibody titers < 10
- Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests
- Current or anticipated use of other investigational agents or marketed anticancer agent while on study
- Patients who have received chemotherapy or radiotherapy within 4 weeks prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who are less than 4 weeks from surgery (except biopsies) or have insufficient recovery from surgical-related trauma or wound healing
- Small pox vaccination for 4 weeks before study therapy and during study treatment
- Have known immune system disorders (including acquired immunodeficiency syndrome [AIDS], HIV infection or hepatitis B or C); eligible patients must have a negative HIV test result within 4 weeks prior to study initiation
- Patients who are receiving additional immunosuppressive therapy or any steroids (except concurrent corticosteroid usage if no more than 20 mg per day, prednisolone equivalent is applied)
- Have received prior gene therapy or therapy with cytolytic virus of any type
- Have clinically significant cardiac disease (New York Heart Association class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction one year prior to study entry, or grade 2 or higher compromised left ventricular ejection fraction
- Oxygen saturation < 90% measured by pulse oximetry at rest
- Have dementia or altered mental status that would prohibit informed consent
- Severe or uncontrolled medical disorder that would, in the investigator’s opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, fever, systemic and/or uncontrolled infections, psychiatric illness/social situations that would limit compliance with study requirements)
- Be receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study
- Have known allergy to ovalbumin or other egg products
- Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) as assessed by the principal investigator during screening and during the study
- Have a history of allergy to iodinated contrast media
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Pregnant or nursing
Locations & Contacts
Trial Objectives and Outline
I. To assess the safety of concurrent administration of the oncolytic virus GL-ONC1 and the complement inhibitor eculizumab in patients with aggressive solid organ cancer prior to undergoing surgery.
I. To assess presence of GL-ONC1 within malignant tumors after bolus intravenous (IV) injection by examination of the resected surgical specimen when applicable.
II. To assess the effect of the complement inhibitor eculizumab on the pharmacokinetics (PK) of GL-ONC1 in circulation and in tumor tissue.
III. To evaluate antitumor effects of GL-ONC1 alone and in combination with the complement inhibitor eculizumab.
IV. To evaluate anti-vaccinia and anti-tumor immune responses following administration of GL-ONC1.
OUTLINE: This is a dose-escalation study of light-emitting oncolytic vaccinia virus GL-ONC1. Patients are assigned to 1 of 2 groups.
GROUP I: Patients receive light-emitting oncolytic vaccinia virus GL-ONC1 IV on days 1-5 of week 1 in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive eculizumab IV over 35 minutes on days 1, 2, or 3 of week 1 and light-emitting oncolytic vaccinia virus GL-ONC1 IV on day 1 or days 1-5 of week 1 in the absence of disease progression or unacceptable toxicity.
In both groups, patients undergoing surgery more than 10 days following virus treatment may receive additional maintenance dose of eculizumab at the discretion of the principal investigator (PI).
After completion of study treatment, patients are followed up for up to 3 years.
Trial Phase & Type
University of California San Diego
Secondary IDs NCI-2016-01782
Clinicaltrials.gov ID NCT02714374