TR-002 for the Treatment of Advanced Unresectable Metastatic Solid Tumors Unresectable or Metastatic, Refractory Pancreatic Adenocarcinoma

Brief summary public domain (ClinicalTrials.gov)

This phase I trial tests the safety, side effects and best dose of TR-002 for the treatment of solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable), that has spread from where it first started (primary site) to other places in the body (metastatic) and unresectable or metastatic pancreatic adenocarcinoma that does not respond to treatment (refractory). Chemotherapy drugs, such as TR-002, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. TR-002 may be safe and tolerable in treating patients with advanced, unresectable or metastatic solid tumors and unresectable or metastatic, refractory pancreatic adenocarcinoma.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), which will also be the recommended phase 2 dose (RP2D) of Nadofaragene Firadenovec (TR-002) for the treatment of advanced treatment-refractory solid tumors. II. To evaluate the toxicities of TR-002 administered intravenous weekly. SECONDARY OBJECTIVES: I. To obtain preliminary assessment of anti-tumor activity of TR-002 administered intravenous weekly at the RP2D. II. To evaluate the pharmacokinetics of TR-002 administered intravenous weekly. EXPLORATORY OBJECTIVE: I. To assess the effects of TR-002 on pharmacodynamic biomarkers relating to the mechanism of action. OUTLINE: This is a dose-escalation study of TR-002 followed by a dose-expansion study. Patients receive TR-002 intravenously (IV), over 1 hour, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or multigated acquisition (MUGA) scan during screening and undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days and every 60 days for 1 year.

Intervention public domain (ClinicalTrials.gov)

Drug: TR-002. Weekly intravenous infusion

Arm public domain (ClinicalTrials.gov)

Treatment (TR-002) (experimental): Patients receive TR-002 IV, over 1 hour, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan during screening and undergo CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of dose limiting toxicity (DLTs). The proportion of DLTs at each dose level will be reported with exact binomial 95% confidence intervals. Time frame: From first dose of TR-002 to day 28.

Primary outcome public domain (ClinicalTrials.gov)

Number of participants experiencing treatment-related adverse events. Classified by severity, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Time frame: From first dose of TR-002 to 90 days following the last dose.

Secondary outcome public domain (ClinicalTrials.gov)

Objective response rate (ORR). Time frame: From the first dose of TR-002 up to 1 year post last dose.

Secondary outcome public domain (ClinicalTrials.gov)

Progression free survival. Time frame: From the date of enrollment until the first occurrence of disease progression, or death from any cause, whichever occurs earlier, up to 1 year post last dose.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival. Time frame: From the date of enrollment until death from any cause, up to 1 year post last dose.

Secondary outcome public domain (ClinicalTrials.gov)

Steady state through concentrations in serum. Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion.

Secondary outcome public domain (ClinicalTrials.gov)

Peak Plasma Concentration (Cmax). Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion.

Secondary outcome public domain (ClinicalTrials.gov)

Area under the serum concentration. Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Aged 18 or over at the time of consent * Pathology or histology-confirmed metastatic or unresectable solid tumor for which standard systemic treatments are no longer effective or not tolerated * For the expansion cohort, participants must have pathology or histology-confirmed metastatic or unresectable pancreatic adenocarcinoma that is refractory and/or intolerant to all standard-of-care systemic treatments (including gemcitabine, nab-paclitaxel, fluoropyrimidine, oxaliplatin, and irinotecan) * Participants in dose escalation may have measurable and/or non-measurable disease. Imaging for disease assessment of measurable and non-measurable disease must be completed within 28 days prior to registration. Participants in dose expansion must have measurable disease per Response Evaluation Criteira in Solid Tumors (RECIST) 1.1 * Adequate cardiac function, assessed by multiple-gated acquisition (MUGA) scan or echocardiography (left ventricular ejection fraction of \> 50%) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Absolute neutrophil count ≥ 1,000/mcL * Platelets ≥ 75,000/mcL * Hemoglobin ≥ 8g/dL * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (\< 3 x ULN in patients with known Gilberts) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN (\< 5 x ULN in patients with known liver metastases) * Creatinine ≤ 1.5 x institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 * For people of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method through 3 months following the last dose of study treatment * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study Exclusion Criteria: * Lactating or pregnant patients or patients of reproductive potential not willing to use effective methods of contraception * Clinically significant toxicities from most recent therapy or intervention prior to study enrollment that have not resolved to baseline or grade 1 (exceptions include alopecia and grade 2 sensory neuropathy) * Participant with a history of the following significant cardiovascular disease will be excluded: * Participant has a history of myocardial infarction or unstable …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 52 participants (estimated).