Ramucirumab and Irinotecan Hydrochloride in Treating Patients with Metastatic or Locally Advanced Gastric or Gastroesophageal Junction Cancer

Status: Active

Description

This phase II trial studies how well ramucirumab and irinotecan hydrochloride work in treating patients with gastric or gastroesophageal junction cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or to other parts of the body (metastatic). Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Irinotecan hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ramucirumab and irinotecan hydrochloride may be a better treatment for patients with metastatic or advanced gastric or gastroesophageal junction cancer.

Eligibility Criteria

Inclusion Criteria

  • Histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma that is metastatic or locally advanced and unresectable
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan (or magnetic resonance imaging [MRI] at the discretion of the principal investigator [PI]), as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam
  • Either primary or non-osseous metastatic site amenable for research biopsy for patients enrolled at Washington University, as confirmed by scheduling of biopsy procedure. Biopsy should be obtained at least 7 days prior to cycle 1 day 1 (C1D1)
  • Experienced documented objective radiographic or clinical disease progression during first-line therapy or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) or taxane (docetaxel) for unresectable or metastatic disease * NOTE: This is not intended to be an exclusive list of allowed agents; the targeted therapies such as Herceptin and ADC, or immunotherapies without cytotoxic chemotherapy, are permitted
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Hemoglobin >= 9.0 g/dL (5.58 mmol/L)
  • Platelets >= 100,000/uL
  • Total bilirubin =< 1.5 mg/dL (25.65 umol/L)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (IULN) (or =< 5.0 x IULN in the setting of liver metastases)
  • Creatinine =< 1.5 x IULN OR creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x IULN (that is, if serum creatinine is > 1.5 x IULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
  • Urinary protein =< 1+ on dipstick or routine urinary analysis (UA); if dipstick or routine UA is >= 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours
  • Adequate coagulation function as defined by international normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) =< 5 seconds above the ULN (unless receiving anticoagulation therapy); patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy
  • All clinically significant toxic effects (except peripheral neuropathy) of prior locoregional therapy, surgery, or other anticancer therapy have resolved to =< CTCAE grade 1
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately; women of childbearing potential must have a negative serum pregnancy test within 7 days of study entry
  • Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

  • Squamous cell or undifferentiated gastric cancer
  • Received any chemotherapy (including irinotecan) other than platinum and fluoropyrimidine with or without anthracycline or taxane for advanced gastric or GEJ adenocarcinoma
  • Received previous systemic chemotherapy with a cumulative dose of > 900 mg/m^2 of epirubicin or > 400 mg/m^2 of doxorubicin
  • Received any previously systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways; other previous targeted therapies are permitted if stopped at least 28 days prior to start of treatment
  • A history of other malignancy =< 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix or other solid tumors treated curatively and without evidence of recurrence
  • Currently receiving any other investigational agents
  • History or evidence of known brain metastases or carcinomatous meningitis; patients with known brain metastases must 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
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to monoclonal antibody treatment, any components used in the ramucirumab drug product (DP) preparation, irinotecan, or other agents used in the study
  • Any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollment
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to enrollment
  • History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port of catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to enrollment
  • History of any arterial thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina within 6 months prior to enrollment
  • Diagnosis of symptomatic congestive heart failure (New York Heart Association [NYHA] II-IV) or symptomatic or poorly controlled cardiac arrhythmia
  • Uncontrolled or poorly controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management
  • Presence of serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment
  • Major surgery within 28 days prior to first dose of protocol therapy
  • Minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy
  • Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents; once-daily aspirin use (maximum dose 325 mg/day) is permitted
  • The patient has elective or planned major surgery to be performed during the course of the clinical trial
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn’s disease, ulcerative colitis, or chronic diarrhea
  • Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis (i.e. ascites from cirrhosis requiring diuretics or paracentesis); patients with ascites not related to cirrhosis, such as malignant ascites, are allowed
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, metabolic disorders or other nonmalignant organ or systemic disease or secondary effects of cancer that induce a high medical risk and make assessment of survival uncertain, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and/or breastfeeding
  • Known human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy

Locations & Contacts

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Albert Craig Lockhart
Phone: 305-243-0116
Email: aclockhart@med.miami.edu
Tampa
Moffitt Cancer Center
Status: Active
Contact: Rutika Mehta
Phone: 813-745-1277
Email: Rutika.Mehta@moffitt.com

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Haeseong Park
Phone: 314-747-7510
Email: haeseongpark@wustl.edu

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Aravind Raj Sanjeevaiah
Phone: 214-645-8300
Email: aravind.sanjeevaiah@utsouthwestern.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine the progression-free survival (PFS) with irinotecan hydrochloride (irinotecan) plus ramucirumab in patients with metastatic gastric and gastro-esophageal junction cancer who have progressed after first line chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the overall survival (OS) of patients treated with irinotecan plus ramucirumab.

II. To determine time to progressive disease (TTP) in patients treated with irinotecan plus ramucirumab.

III. To determine the best overall response (BOR) of confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) or progressive disease (PD) in patients treated with irinotecan plus ramucirumab.

IV. To determine the objective response rate (ORR) (defined as confirmed CR + confirmed PR) in patients treated with irinotecan plus ramucirumab.

V. To determine clinical benefit rate (CBR) (percentage of combined patients who have achieved confirmed CR, confirmed PR and SD) in patients treated with irinotecan plus ramucirumab.

VI. To evaluate toxicity and tolerability of irinotecan plus ramucirumab as measured by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.

EXPLORATORY OBJECTIVES:

I. To determine the success rate of patient-derived xenograft (PDX)/patient-derived organoid (PDO) generation from patients with metastatic gastroesophageal cancer.

II. To evaluate the responses to treatment with ramucirumab and irinotecan in PDX/PDO models.

III. To characterize molecular changes in PDX/PDO models along with corresponding patients’ clinical courses to identify potential predictors of response and mechanism of resistance.

IV. To investigate changes blood based angiome profile and cell free deoxyribonucleic acid (DNA) in patients following treatment with ramucirumab and irinotecan to identify potential mechanism of response and resistance.

OUTLINE:

Patients receive ramucirumab intravenously (IV) over 60 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 18 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Haeseong Park

Trial IDs

Primary ID 201704082
Secondary IDs NCI-2017-00700
Clinicaltrials.gov ID NCT03141034