| Protocol No. | UW19029 |
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|---|---|---|---|
| Principal Investigator | Uboha, Nataliya | ||
| Phase | II | ||
| Age Group | Adult | ||
| ClinicalTrials.Gov | NCT04150640 (Click to jump to clinicaltrials.gov) | ||
| Management Group(s) | Gastrointestinal; UWCCC 1 South Park; _External Institution(s) | ||
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Title
Description
Objective
Cohort 1: Objective Response Rate (ORR) [ Time Frame: up to 1 year ] ORR will be calculated by combining the number of participants who achieve complete response and partial response per RECIST 1.1 criteria, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). An ORR of 40% or less for proposed combination of 5-Fluorouracil, Oxaliplatin and nal-IRI during 1st line treatment of advanced esophageal and gastric adenocarcinoma in HER2-negative subjects will be considered as unacceptably low. The number and frequencies of objectives responses will be summarized in tabular format. The ORR will be reported along with the corresponding one-sided 90% confidence intervals. Cohort 2: Incidence of Adverse Events [ Time Frame: up to 1 year ] The primary objective of cohort 2 (HER2-positive EGA) is to evaluate safety and tolerability of the studied drug combination. Toxicities and adverse events will be summarized by type and severity in tabular format. Secondary Outcome Measures: Progression Free Survival (PFS) [ Time Frame: up to 2 years ] PFS will be defined from the date study enrollment to the date of progression event or death. If a participant does not experience a progression event at the end of the follow-up period, then the PFS will be censored at the last assessment date. PFS will be analyzed using the Kaplan-Meier method. Median PFS will be reported along with the corresponding 90% confidence interval which will be constructed using the nonparametric Brookmeyer-Crooley method. Disease Control Rate (DCR) [ Time Frame: up to 1 year ] The DCR is the proportion of all participants with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).DCR will be reported along with the corresponding 90% confidence intervals which will be constructed using the Wilson score method. Progression Free Survival at 6 months [ Time Frame: up to 6 months ] PFS will be defined from the date study enrollment to the date of progression event or death. If a participant does not experience a progression event at the end of the follow-up period, then the PFS will be censored at the last assessment date. PFS will be analyzed using the Kaplan-Meier method. Median PFS will be reported along with the corresponding 90% confidence interval which will be constructed using the nonparametric Brookmeyer-Crooley method. Progression Free Survival at 12 months [ Time Frame: up to 1 year ] PFS will be defined from the date study enrollment to the date of progression event or death. If a participant does not experience a progression event at the end of the follow-up period, then the PFS will be censored at the last assessment date. PFS will be analyzed using the Kaplan-Meier method. Median PFS will be reported along with the corresponding 90% confidence interval which will be constructed using the nonparametric Brookmeyer-Crooley method. Cohort 1: Incidence of Adverse Events [ Time Frame: up to 1 year ] Toxicities and adverse events will be summarized in tabular format, stratified by type and severity Cohort 2: Overall Response Rate [ Time Frame: up to 1 year ] ORR will be calculated by combining the number of participants who achieve complete response and partial response per RECIST 1.1 criteria, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
Treatment
Experimental: Cohort 1: HER2 Negative
Key Eligibility Inclusion Criteria: Written informed consent and HIPAA authorization for release of personal health information. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Histological or cytological confirmed locally advanced or metastatic EGA. Known HER2 status prior to treatment initiation required. Measurable disease according to RECIST v1.1. No prior lines of systemic therapy for advanced disease. Participants who had received neoadjuvant or adjuvant therapy or definitive chemoradiation will be allowed to participate if recurrence occurred 6 months or longer from the completion of all prior treatments. Demonstrate adequate organ function as defined below; all screening labs to be obtained within 14 days prior to registration Absolute Neutrophil Count (ANC) greater than or equal to 1,500 /μl without the use of hematopoietic growth factors Hemoglobin (Hgb) greater than or equal to 8 g/dL (blood transfusions are permitted for participants with hemoglobin levels below 8 g/dL) Platelets greater than or equal to 100,000 /μl Serum creatinine greater than or equal to 1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl). CrCl calculation using the Cockcroft-Gault formula. greater than or equal to 50 mL/min for participants with creatinine levels > 1.5 X institutional ULN Bilirubin within normal range for the institution (biliary drainage is allowed for biliary obstruction) Aspartate aminotransferase (AST) less than or equal to 2.5 X ULN OR less than or equal to 5 X ULN for subjects with liver metastases Alanine aminotransferase (ALT) less than or equal to 2.5 X ULN OR less than or equal to 5 X ULN for subjects with liver metastases Albumin >3.0 g/dL International Normalized Ratio (INR) or Prothrombin Time (PT) less than or equal to1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Women of childbearing potential should have a negative urine or serum pregnancy test within 14 days of study registration. NOTE: Women are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months Women of childbearing potential and males must be willing to abstain from heterosexual activity or to use a form of effective method of contraception from the time of informed consent until 30 days after treatment discontinuation. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Applicable Disease Sites
Participating Institutions
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