Clinical Trials /

Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery

NCT02520141

Description:

This phase II trial studies how well ramucirumab works in treating patients with previously treated biliary cancers that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery. 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.

Related Conditions:
  • Cholangiocarcinoma
  • Gallbladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery
  • Official Title: A Phase II Study of Ramucirumab for Advanced, Pre-Treated Biliary Cancers

Clinical Trial IDs

  • ORG STUDY ID: 2015-0393
  • SECONDARY ID: NCI-2015-01442
  • SECONDARY ID: 2015-0393
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02520141

Conditions

  • Cholangiocarcinoma
  • Liver and Intrahepatic Bile Duct Carcinoma
  • Stage III Gallbladder Cancer AJCC v7
  • Stage III Intrahepatic Cholangiocarcinoma AJCC v7
  • Stage IIIA Gallbladder Cancer AJCC v7
  • Stage IIIB Gallbladder Cancer AJCC v7
  • Stage IV Gallbladder Cancer AJCC v7
  • Stage IVA Gallbladder Cancer AJCC v7
  • Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7
  • Stage IVB Gallbladder Cancer AJCC v7
  • Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7
  • Unresectable Gallbladder Carcinoma

Interventions

DrugSynonymsArms
Ramucirumabanti-VEGFR-2 fully human monoclonal antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2Treatment (ramucirumab)

Purpose

This phase II trial studies how well ramucirumab works in treating patients with previously treated biliary cancers that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery. 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the progression-free survival (PFS) of ramucirumab in advanced biliary cancers
      (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer)
      who have received prior chemotherapy.

      SECONDARY OBJECTIVES:

      I. Determine the response rate (RR) and disease control rate (partial response + complete
      response + stable disease) of ramucirumab in advanced biliary cancers.

      II. Determine overall survival (OS) of ramucirumab in advanced biliary cancers. III. Evaluate
      the toxicity of ramucirumab in advanced biliary cancers.

      EXPLORATORY OBJECTIVES:

      I. Correlate the carbohydrate antigen (CA) 19-9 response (defined as > 50% decrease from
      baseline) with tumor response, PFS and OS.

      II. Correlate baseline tumor gene expression profile with PFS. III. Correlate pre- and
      post-therapy computed tomography (CT) imaging to quantify iodine content, atomic numbers, and
      Z-values and correlate with response.

      OUTLINE:

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

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ramucirumab)ExperimentalPatients receive ramucirumab IV over 60 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Ramucirumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have cholangiocarcinoma, gallbladder cancer or adenocarcinoma on liver
             biopsy with clinical features consistent with biliary primary/cholangiocarcinoma

          -  Metastatic or unresectable disease documented on diagnostic imaging studies

          -  Must have received at least one regimen containing gemcitabine chemotherapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Total bilirubin =< 1.5 mg/dL (25.65 mol/L)

          -  Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3.0 times the upper
             limit of normal ([ULN]; or 5.0 times the ULN in the setting of liver metastases)

          -  Absolute neutrophil count (ANC) >= 1000/uL

          -  Hemoglobin >= 9 g/dL (5.58 mmol/L)

          -  Platelets >= 100,000/uL

          -  The patient does not have:

               -  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; clinically meaningful ascites is
                  defined as ascites from cirrhosis requiring diuretics or paracentesis

          -  Serum creatinine =< 1.5 times the ULN or

          -  Creatinine clearance (measured via 24-hour urine collection) >= 40 mL/minute (that is,
             if serum creatinine is > 1.5 times the ULN, a 24-hour urine collection to calculate
             creatinine clearance must be performed

          -  The patient's urinary protein is =< 1 positive (+) (=< 30-100 mg/dl) on dipstick or
             routine urinalysis (urinary analysis [UA]; if urine dipstick or routine analysis is >=
             2+ (>=100-300 mg/dl), a 24-hour urine collection for protein must demonstrate < 1000
             mg of protein in 24 hours to allow participation in this protocol)

          -  The patient must have adequate coagulation function as defined by international
             normalized ratio (INR) =< 1.5 and

          -  Partial thromboplastin time (PTT) (PTT/activated partial thromboplastin time [aPTT]) <
             1.5 x ULN)

          -  Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14
             days) of oral anticoagulant or low molecular weight heparin; if receiving warfarin,
             the patient must have an INR =< 3.0 and no active bleeding (that is, no bleeding
             within 14 days prior to first dose of protocol therapy) or pathological condition
             present that carries a high risk of bleeding (for example, tumor involving major
             vessels or known varices)

          -  The patient, if sexually active, must be postmenopausal, surgically sterile, or using
             effective contraception (hormonal or barrier methods)

          -  Female patients of childbearing potential must have a negative serum pregnancy test
             within 7 days

          -  Patients must sign an informed consent and authorization indicating that they are
             aware of the investigational nature of this study and the known risks involved

          -  In the ten patient expanded cohort, patients diagnosed with deoxyribonucleic acid
             (DNA) repair or FGFR genetic aberrations will be enrolled

        Exclusion Criteria:

          -  The patient has experienced any grade 3-4 gastrointestinal (GI) bleeding within 3
             months prior to enrollment

          -  Prior therapy with any agent targeting the vascular endothelial growth factor receptor
             (VEGFR) pathway to include bevacizumab, pazopanib, and other anti-angiogenesis
             inhibitors

          -  The patient has a history of deep vein thrombosis, pulmonary embolism, or any other
             significant thromboembolism, including portal venous thrombosis (venous port or
             catheter thrombosis, incidental pulmonary embolism diagnosed on imaging studies or
             superficial venous thrombosis are not considered significant) during the 3 months
             prior to randomization

          -  The patient has experienced any arterial thromboembolic events, including but not
             limited to myocardial infarction, transient ischemic attack, cerebrovascular accident,
             or unstable angina, within 6 months prior to enrollment

          -  The patient has uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or
             > 100 mmHg diastolic for > 4 weeks) despite standard medical management

          -  The patient has a serious or non-healing wound, ulcer, or bone fracture within 28 days
             prior to enrollment

          -  The patient has undergone major surgery within 28 days prior to enrollment, or
             subcutaneous venous access device placement within 7 days prior to enrollment

          -  The patient is 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

          -  The patient is pregnant or breast-feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival of ramucirumab in advanced biliary cancers
Time Frame:From the date of treatment start to the date of disease progression or to the date of death, whichever occurs first, or to the last follow-up date if patients are alive without disease progression, assessed up to at least 3 months post-treatment
Safety Issue:
Description:Progression free survival is measured using 95% confidence intervals.

Secondary Outcome Measures

Measure:Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 28 days
Safety Issue:
Description:Unacceptable toxicities will also be monitored closely for the study drug using the method of Thall et al (1995).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated