Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ramucirumab Plus Irinotecan for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03141034
Recruitment Status : Recruiting
First Posted : May 4, 2017
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The investigators hypothesize that this combination regimen of irinotecan plus ramucirumab administered as second line treatment will be tolerated and lead to improved outcomes similar to paclitaxel plus ramucirumab in patients with advanced gastric and gastro-esophageal junction (GEJ) cancers. This study proposes a phase II clinical trial with irinotecan plus ramucirumab for treatment of patients with metastatic gastric and GEJ adenocarcinoma who have progressed after first line chemotherapy. To the knowledge of the investigators, this regimen has not been previously administered to this patient population, so safety and tolerability will be monitored and reported.

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Gastro-esophageal Junction Adenocarcinoma Drug: Irinotecan Drug: Ramucirumab Genetic: Blood for angiome profiling Genetic: Blood for cfDNA Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ramucirumab Plus Irinotecan in Patients With Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020


Arm Intervention/treatment
Experimental: Irinotecan plus ramucirumab
-Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Drug: Irinotecan
-Irinotecan is commercially available and will be billed to insurance.
Other Names:
  • Camptosar®
  • CPT-11

Drug: Ramucirumab
-Ramucirumab will be provided free of charge by Eli Lilly and Company.
Other Name: Cyramza®

Genetic: Blood for angiome profiling
-Before treatment on cycle 1 day 1, cycle 5 day 1, cycle 9 day 1, and end of treatment

Genetic: Blood for cfDNA
-Before treatment on cycle 1 day 1, cycle 3 day 1, cycle 5 day 1, cycle 7 day 1, cycle 9 day 1, and end of treatment




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months) ]
    -PFS will be measured from date of study entry to first radiographic progression or death due to any cause. Radiographic progressive disease (PD) will be defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). For those who are alive and do not experience progression, the investigators will censor them at the time of loss to follow-up (very few) or at 12 months from the study entry, whichever comes first.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months) ]
    -OS time will be measured from date of study entry to date of death from any cause. For those who are alive, the investigators will censor them at the time of loss to follow-up (very few) or at 12 months from the study entry, whichever comes first.

  2. Time to progressive disease (TTP) [ Time Frame: Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months) ]
    -TTP is defined as the time from study entry until date of radiographic PD using RECIST v1.1 criteria. For those who are alive and do not experience progression, the investigators will censor them at the time of loss to follow-up (very few) or at 12 months from the study entry, whichever comes first. For those who are dead before progression, the investigators will consider death as the competing risk. If the number of death are very small, the investigators will censor them at time of death.

  3. Best overall response (BOR) [ Time Frame: Up to end of treatment (estimated to be 6 months) ]
    -BOR is defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR is defined as having a ≥30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. SD was defined as small changes that did not meet above criteria.

  4. Objective response rate (ORR) [ Time Frame: Up to end of treatment (estimated to be 6 months) ]
    -ORR defined as confirmed complete response + confirmed partial response

  5. Clinical benefit rate (CBR) [ Time Frame: Up to end of treatment (estimated to be 6 months) ]
    -CBR defined as percentage of combined participants who have achieved confirmed complete response, confirmed partial response, and stable disease

  6. Toxicity and tolerability of regimen as measured by the count of the worst grade of adverse event experienced by each participant [ Time Frame: Up to 30 days following completion of treatment (estimated to be 7 months) ]
    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 CT scan (or MRI at the discretion of the principal investigator (PI)), as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • 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.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count (ANC) ≥ 1,500/µL
    • Hemoglobin ≥ 9.0 g/dL (5.58 mmol/L)
    • Platelets ≥ 100,000/µL
    • Total bilirubin ≤ 1.5 mg/dL (25.65 µmol/L)
    • AST(SGOT)/ALT(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 m2 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 urinalysis (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 INR ≤ 1.5 and 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 ≤ Common Terminology Criteria for Adverse Events (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 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 DP preparation, irinotecan, or other agents used in the study.
  • Any grade 3-4 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 (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 anti-inflammatory 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).
  • 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 HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with ramucirumab and irinotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03141034


Contacts
Layout table for location contacts
Contact: Haeseong Park, M.D., MPH (314) 747-7401 haeseongpark@wustl.edu

Locations
Layout table for location information
United States, Florida
University of Miami - Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Albert C Lockhart, M.D.    305-243-0116    aclockhart@med.miami.edu   
Principal Investigator: Albert C Lockhart, M.D.         
Sub-Investigator: Bach Ardalan, M.D.         
Sub-Investigator: Peter J Hosein, M.D.         
Sub-Investigator: Agustin Pimentel, M.D.         
H. Lee Moffitt Cancer Center and Research Institute, Inc. Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Rutika Mehta, M.D.    813-745-1277    rutika.mehta@moffitt.com   
Principal Investigator: Rutika Mehta, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Haeseong Park, M.D, MPH    314-747-7401    haeseongpark@wustl.edu   
Principal Investigator: Haeseong Park, M.D., MPH         
Sub-Investigator: Manik Amin, M.D,         
Sub-Investigator: Eric Knoche, M.D.         
Sub-Investigator: Kian Lim, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Katrina Pederson, M.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: Andrea Wang-Gillam, M.D.         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Aravind Sanjeevaiah, M.D.    214-645-8300      
Principal Investigator: Aravind Sanjeevaiah, M.D.         
Sub-Investigator: Muhammad Beg, M.D.         
Sub-Investigator: Leticia Khosama, N.P.         
Sub-Investigator: Udit Verma, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Eli Lilly and Company
Investigators
Layout table for investigator information
Principal Investigator: Haeseong Park, M.D., MPH Washington University School of Medicine

Additional Information:
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03141034     History of Changes
Other Study ID Numbers: 201704082
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Irinotecan
Ramucirumab
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents