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

STATUS

Recruiting
End date

Dec 13, 2026
participants needed

52
sponsor

University of Wisconsin, Madison

Send

Updated on 13 May 2022

See if I qualify

combinations

hysterectomy

systemic therapy

measurable disease

anticoagulants

fluorouracil

oophorectomy

international normalized ratio

combination chemotherapy

oxaliplatin

neutrophil count

HER2

irinotecan

blood transfusion

trastuzumab

aptt

thromboplastin

adenocarcinoma

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.

Description

Participants will be enrolled into one of four cohorts. Participants in Cohort 1 (HER-2 negative) will receive 5-FU, oxaliplatin and nal-IRI. Cohort 3 (HER-2 negative) will use nivolumab in addition to 5-FU, oxaliplatin and nal-IRI. Participants in Cohort 2 (HER-2 positive) will receive trastuzumab in addition to 5-FU, oxaliplatin and nal-IRI. Cohort 4 (HER-2 positive) will also include pembrolizumab in addition to trastuzumab, 5-FU, oxaliplatin and nal-IRI.

Chemotherapy doses will be the same for all cohorts and will follow similar modifications for toxicities. Agents will be administered as per institutional standards when similar regimens (such as FOLFIRINOX, FOLFOX, and trastuzumab) are used.

Cohort 1 (HER2-negative tumors): Up to 13 evaluable participants will be accrued to Cohort 1.

Cohort 2 (HER2-positive tumors): Up to a total of 6 subjects will be enrolled to evaluate the safety and tolerability of the proposed 5-Fluorouracil, Oxaliplatin and liposomal Irinotecan combination in HER2-positive subjects.

Cohort 3 (HER-2 negative tumors):12 participants will be enrolled during stage 1. If at most 5 objective responses per RECIST 1.1 are observed, then further enrollment will be halted. Otherwise, 15 additional participants will be enrolled for a total number of 27.

Cohort 4 (HER-2 positive tumors): treated with oxaliplatin, Nal-IRI and trastuzumab in combination with pembrolizumab. A total of up to 6 subjects will be accrued to evaluate safety and tolerability.

Details

Condition	Esophageal Adenocarcinoma, Gastric Adenocarcinoma
Treatment	Trastuzumab, Pembrolizumab, Oxaliplatin, 5-FU, nal-IRI, Nivolumab
Clinical Study Identifier	NCT04150640
Sponsor	University of Wisconsin, Madison
Last Modified on	13 May 2022

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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
	Albumin >3.0 g/dL
	International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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
	Activated Partial Thromboplastin Time (aPTT) ≤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
	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
	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
Exclusion Criteria
	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
	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
	Active infection requiring systemic therapy
	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.)
	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
	Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion
	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
	NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
	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)
	Known history of Human Immunodeficiency Virus (HIV)
	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

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

0/250

By sending a message, I agree that my data will be sent to a representative for the selected site and processed in accordance with this website's Privacy Policy (see link in footer).

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

international normalized ratio

combination chemotherapy

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Edit Delete

Added by •

•

Private

Edit Delete

Reply by • • Private

Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

Enter the passcode

The passcode will expire in None.

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