Clinical Trials /

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

NCT03141034

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ramucirumab Plus Irinotecan for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma
  • Official Title: Ramucirumab Plus Irinotecan in Patients With Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 201704082
  • NCT ID: NCT03141034

Conditions

  • Gastric Adenocarcinoma
  • Gastro-esophageal Junction Adenocarcinoma

Interventions

DrugSynonymsArms
IrinotecanCamptosar®, CPT-11Irinotecan plus ramucirumab
RamucirumabCyramza®Irinotecan plus ramucirumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Irinotecan plus ramucirumabExperimental-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.
  • Irinotecan
  • Ramucirumab

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months)
Safety Issue:
Description:-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

Measure:Overall survival (OS)
Time Frame:Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months)
Safety Issue:
Description:-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.
Measure:Time to progressive disease (TTP)
Time Frame:Up to 18 months from completion of treatment (estimated median treatment and follow-up of 10 months)
Safety Issue:
Description:-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.
Measure:Best overall response (BOR)
Time Frame:Up to end of treatment (estimated to be 6 months)
Safety Issue:
Description:-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.
Measure:Objective response rate (ORR)
Time Frame:Up to end of treatment (estimated to be 6 months)
Safety Issue:
Description:-ORR defined as confirmed complete response + confirmed partial response
Measure:Clinical benefit rate (CBR)
Time Frame:Up to end of treatment (estimated to be 6 months)
Safety Issue:
Description:-CBR defined as percentage of combined participants who have achieved confirmed complete response, confirmed partial response, and stable disease
Measure: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)
Safety Issue:
Description:-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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

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