Oxaliplatin and Liposomal Irinotecan (Plus Trastuzumab for HER2-positive Disease) in Advanced Esophageal and Gastric Adenocarcinoma

NCT04150640 | Recruiting Phase 2 DMC FDA Drug

• 6 other identifiers: UW19029NCI-2019-07966A534260SMPH/MEDICINE/HEM-ONC2019-0632Protocol Version 7/1/2024
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, phase II, multi-site trial evaluating the efficacy and safety of the combination of 5-FU, oxaliplatin, nal-IRI, and immunotherapy (plus trastuzumab for HER2-positive tumors) as first-line therapy for participants with advanced Esophageal and Gastric Adenocarcinoma (EGA). The investigators hypothesize that this drug combination will be better tolerated than current first-line chemotherapy combinations for this disease.

Conditions

Esophageal Adenocarcinoma; Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Cohort 1: Objective Response Rate (ORR)

  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.

  up to 1 year

• Cohort 3: Objective Response Rate (ORR)

  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 45% or less for proposed combination of 5-Fluorouracil, Oxaliplatin, nal-IRI and Nivolumab 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.

  up to 1 year

• Cohorts 2 and 4: Incidence of Adverse Events

  The primary objective of cohorts 2 and 4 (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.

  up to 1 year

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  up to 2 years

• Disease Control Rate (DCR)

  up to 1 year

• Progression Free Survival at 6 months

  up to 6 months

• Progression Free Survival at 12 months

  up to 1 year

• Cohorts 1 and 3: Incidence of Adverse Events

  up to 1 year

Study Arms (4)

Cohort 1: HER2 Negative

EXPERIMENTAL

Participants in Cohort 1 (HER2-negative) will be treated with nal-IRI (50 mg/m\^2 - intravenously over 90 min), 5-FU (2400 mg/m\^2 over 46 hrs), and oxaliplatin (60 mg/m\^2). Each cycle is 28 days. Participants will receive treatments on day 1 and 15 of each cycle.

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: 5-FU

Cohort 2: HER2 Positive

EXPERIMENTAL

Participants in Cohort 2 (HER2-positive) will be treated with nal-IRI (50 mg/m\^2 - intravenously over 90 min), trastuzumab (6 mg/kg C1D1, then 4 mg/kg on each subsequent treatment days), 5-FU (2400 mg/m\^2 over 46 hrs), and oxaliplatin (60 mg/m\^2). Each cycle is 28 days. Participants will receive treatments on day 1 and 15 of each cycle.

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: 5-FU; Drug: Trastuzumab

Cohort 3: HER2 Negative

EXPERIMENTAL

Participants in Cohort 3 (HER2-negative) will be treated with nal-IRI (50 mg/m\^2 - intravenously over 90 min), 5-FU (2400 mg/m\^2 over 46 hrs), oxaliplatin (60 mg/m\^2), and nivolumab. (240 mg). Each cycle is 28 days. Participants will receive treatments on day 1 and 15 of each cycle

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: 5-FU; Drug: Nivolumab

Cohort 4: HER2 Positive

EXPERIMENTAL

Participants in Cohort 4 (HER2-positive) will be treated with nal-IRI (50 mg/m\^2 - intravenously over 90 min), trastuzumab (6 mg/kg C1D1, then 4 mg/kg on each subsequent treatment days), 5-FU (2400 mg/m\^2 over 46 hrs), oxaliplatin (60 mg/m\^2), and pembrolizumab (400 mg). Each cycle is 42 days. Participants will receive chemotherapy and trastuzumab treatments on day 1, 15, and 29 of each cycle. Pembrolizumab will be given on day 1 of each cycle.

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: 5-FU; Drug: Trastuzumab; Drug: Pembrolizumab

Interventions

Nal-IRI DRUG

chemotherapy drug

Also known as: liposomal irinotecan

Cohort 1: HER2 Negative; Cohort 2: HER2 Positive; Cohort 3: HER2 Negative; Cohort 4: HER2 Positive

Oxaliplatin DRUG

chemotherapy drug

Cohort 1: HER2 Negative; Cohort 2: HER2 Positive; Cohort 3: HER2 Negative; Cohort 4: HER2 Positive

5-FU DRUG

chemotherapy drug

Also known as: Fluorouracil

Cohort 1: HER2 Negative; Cohort 2: HER2 Positive; Cohort 3: HER2 Negative; Cohort 4: HER2 Positive

Trastuzumab DRUG

immunotherapy

Cohort 2: HER2 Positive; Cohort 4: HER2 Positive

Pembrolizumab DRUG

immunotherapy

Cohort 4: HER2 Positive

Nivolumab DRUG

immunotherapy

Cohort 3: HER2 Negative

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information.
• NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• 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. Known PDL1 CPS status prior to treatment initiation.
• 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) ≥1,500 /μl without the use of hematopoietic growth factors
• Hemoglobin (Hgb) ≥8 g/dL (blood transfusions are permitted for participants with hemoglobin levels below 8 g/dL)
• Platelets ≥100,000 /μl
• Serum creatinine ≤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. ≥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) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

You may not qualify if:

• Known hypersensitivity to 5-FU, oxaliplatin or other platinum agents, or any of the components of nal-IRI and other liposomal products.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not required prior to enrollment).
• Other active malignancy requiring treatment within the last 2 years. Exceptions include subjects with non-melanoma skin cancer, non-invasive/in situ cancer or low-risk prostate cancer requiring hormonal therapy only.
• Current therapy with other investigational agents or participation in another clinical study (supportive care and nontherapeutic trial participation allowed if not receiving an investigational drug). Participants may participate in prescreening for other therapeutic trials (prescreening of biologic sample for specific mutations, receptors, etc.)
• Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment, except for tumor biopsy or placement of central infusion device (port placement).
• Radiotherapy less than 7 days prior to the start of the study treatment
• Participants who receive nivolumab or pembrolizumab in addition to chemotherapy should not have any contraindications to immune checkpoint inhibitors and should not have received immunotherapy agents for the treatment of EGA prior to study enrollment.
• Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years. Participants are permitted to receive immunotherapy l if they have 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 (precipitating event).
• Participants must not have a condition requiring systemic treatment with either corticosteroids (\>10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study immunotherapy administration. Inhaled or topical steroids and adrenal replacement doses (≤10 mg/day prednisone equivalent) are permitted. Participants with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents.
• Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
• Known history of Human Immunodeficiency Virus (HIV).

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Ipsen: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

irinotecan sucrosofate; Oxaliplatin; Fluorouracil; Trastuzumab; pembrolizumab; Nivolumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nataliya Uboha, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

(800) 622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 5, 2019
• Study Start: July 13, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 24, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)