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

NCT03141034 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201704082
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

Gastric Adenocarcinoma; Gastro-esophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  -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 or at 30 months from the study entry, whichever comes first.

  Up to 30 months from completion of treatment (up to 36 months)

Secondary Outcomes (6)

• Overall Survival (OS)

  Up to 30 months from completion of treatment (estimated to be 36 months)

• Time to Progressive Disease (TTP)

  Up to 30 months from completion of treatment (estimated to be 36 months)

• Best Overall Response (BOR)

  Up to end of treatment (estimated to be 6 months)

• Objective Response Rate (ORR)

  Up to end of treatment (estimated to be 6 months)

• Clinical Benefit Rate (CBR)

  Up to end of treatment (estimated to be 6 months)

Study Arms (1)

Irinotecan plus ramucirumab

EXPERIMENTAL

-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; Drug: Ramucirumab; Genetic: Blood for angiome profiling; Genetic: Blood for cfDNA

Interventions

Irinotecan DRUG

-Irinotecan is commercially available and will be billed to insurance.

Also known as: Camptosar®, CPT-11

Irinotecan plus ramucirumab

Ramucirumab DRUG

-Ramucirumab will be provided free of charge by Eli Lilly and Company.

Also known as: Cyramza®

Irinotecan plus ramucirumab

Blood for angiome profiling GENETIC

-Before treatment on cycle 1 day 1, cycle 5 day 1, cycle 9 day 1, and end of treatment

Irinotecan plus ramucirumab

Blood for cfDNA GENETIC

-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

Irinotecan plus ramucirumab

Eligibility Criteria

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

You may qualify if:

• 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.
• Either primary or non-osseous metastatic site amenable for research biopsy for patients enrolled at Washington University, if safe and feasible, as confirmed by scheduling of biopsy procedure. Other methods to obtain appropriate cancer cells such as large-volume paracentesis or thoracentesis can be allowed at PI discretion. Biopsy or other procedures should be performed at least 7 days prior to 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator

Study Sites (4)

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

Irinotecan; Ramucirumab; Blood Specimen Collection; Cell-Free Nucleic Acids

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Kian-Huat Lim, M.D., Ph.D.
• Organization: Washington University School of Medicine

kian-huat.lim@wustl.edu

314-362-6157

Study Officials

• Kian-Huat Lim, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 4, 2017
• Study Start: November 1, 2017
• Primary Completion: April 14, 2023
• Study Completion: April 14, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)