A Study to Evaluate Ramucirumab Plus Trifluridine/Tipiracil to Treat Patients with Previously-treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma

Overview

About this study

The purpose of this study is to compare, in a non-inferiority fashion, the progression-free survival (PFS) in patients with metastatic refractory gastric/Gastroesophageal Junction (GEJ) adenocarcinoma receiving the combination of ramucirumab with TAS-102 vs. paclitaxel and ramucirumab.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Registration:

  • Age ≥ 18 years.
  • Histological or cytological confirmation of adenocarcinoma of the stomach or gastroesophageal junction.
  • Have locally advanced unresectable or metastatic disease that has progressed ≤ 180 days since last treatment.
  • One or more measurable or nonmeasurable evaluable lesions per RECIST
  • Planned for second line treatment defined by failing or were intolerant to previous standard chemotherapies containing one or more of the following agents:
  • fluoropyrimidine (IV 5-FU or capecitabine) and platinum (cisplatin or oxaliplatin);
  • Trastuzumab in case of HER2-positive disease.
    • NOTE: For the patients whose disease recurred ≤ 168 days from the last dose of adjuvant anticancer chemotherapy, that adjuvant anticancer chemotherapy is counted as 1 prior chemotherapy line.
  • ECOG Performance Status (PS) 0 or 1.
  • Ability to swallow oral medications.
  • The following laboratory values obtained ≤ 7 days prior to registration:
    • Absolute neutrophil count (ANC) ≥1500/mm^3;
    • Platelet count ≥ 100,000/mm^3;
    • Hemoglobin ≥ 9.0 g/dL;
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
    • Aspartate transaminase (AST) and alanine transaminase (ALT)  ≥ 3 x ULN ( ≤ 5.0 x UNL, if with liver metastasis).;
    • Coagulation:  Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
      • NOTE: Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
      • NOTE: Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH).
      • EXCEPTION: If receiving warfarin, the patient must have an INR ≤ 3.0. For heparin and LMWH there should be 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).
  • Urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate ≤ 1000 mg of protein in 24 hours to allow participation in this protocol).
  • 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).
  • Cockcroft-Gault Equation:
  • Creatinine clearance for males =      (140 - age)(weight in kg)          
  •                                                           ( 72)(serum creatinine in mg/dL)
  •  
  • Creatinine clearance for females =   (140 - age)(weight in kg)(0.85)
  •                                                           ( 72)(serum creatinine in mg/dL)
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
  • Ability to complete questionnaire(s) by themselves or with assistance.
  • Provide informed written consent ≤28 days prior to registration.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Because the teratogenicity of ramucirumab is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods.

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant women;
    • Nursing women;
    • Women of childbearing potential who are unwilling to employ adequate contraception.
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Previous treatment with TAS-102 or ramucirumab.
  • Previous taxane therapy ≤ 180 days prior to registration.
  • Any grade 3-4 GI bleeding ≤ 90 days prior to registration.
  • History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) ≤ 90 days prior to registration.
  • Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, ≤ 180 days prior to registration.
  • Prior history of GI perforation/fistula ≤ 180 days of registration or risk factors for perforation.
  • Serious or nonhealing wound, ulcer, or bone fracture ≤ 28 days prior to registration.
  • Major surgery ≤ 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement ≤ 7 days prior to registration. 
  • Elective or planned major surgery to be performed during the course of the clinical trial.
  • 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.
    • NOTE: Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
  • Uncontrolled or poorly-controlled hypertension (≥ 160 mmHg systolic or ≥ 100 mmHg diastolic for ≥ 4 weeks) despite standard medical management.
  • Immunocompromised and known to be HIV positive and currently receiving antiretroviral therapy.
    • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
  • Other active malignancy ≤ 3 years prior to registration.
    • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
  • Receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents.
    • NOTE: Once-daily aspirin use (maximum dose 325 mg/day) is permitted.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mohamad Sonbol, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Jason Starr, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions