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TAS 102 and Ramucirumab in Treating Patients with Stage IV or Recurrent Gastric or Gastroesophageal Junction Cancer

Trial Status: Active

This phase II trial studies the side effects and how well TAS 102 and ramucirumab work in treating patients with gastric or gastroesophageal junction cancer that is stage IV or that has come back (recurrent). TAS 102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving TAS 102 and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer.

Inclusion Criteria

  • Histologically confirmed diagnosis of gastric and GEJ adenocarcinoma
  • Measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Stage IV or recurrent disease is required. An irradiated lesion is considered evaluable only if it has shown enlargement since the completion of last radiation
  • Patients must have received and progressed with prior therapy. Prior therapy with ramucirumab is not allowed. Patients must have recovered from the toxic effects of the previous anti-cancer chemotherapy (with the exception of alopecia)
  • Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
  • Estimated life expectancy > 3 months
  • Hemoglobin > 8.0 g/dl
  • Absolute neutrophil count (ANC) > 1,000/mm^3 independent of growth factor support
  • Platelet count > 100,000/mm^3
  • Total bilirubin < 1.5 times ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal (ULN) (=< 5 x ULN for patients with liver involvement)
  • Creatinine clearance >= 30 ml/min
  • Patients must not have had chemotherapy, major surgery, monoclonal antibody therapy or experimental therapy within the 28 days prior to the start of TAS 102 administration
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 4 months for both females and males after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
  • Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study requirements

Exclusion Criteria

  • Subjects with active central nervous system (CNS) metastases are excluded. If CNS metastases are treated and subjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment
  • Women who are pregnant or breast-feeding
  • Prior therapy with ramucirumab, bevacizumab, regorafenib or TAS 102
  • Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]
  • Uncontrolled hypertension (systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mmHg on repeated measurement despite optimal medical management)
  • Any hemorrhage or bleeding event >= National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 within 4 weeks prior to start of study medication
  • Persistent proteinuria >= grade 3 on repeated measurement
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results
  • Subjects with an arterial thrombotic or thromboembolic event within 12 months of informed consent
  • Ascites, pleural effusion, or pericardial fluid requiring drainage in the last 4 weeks
  • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
  • Clinically significant cardiovascular disease such as unstable angina, uncontrolled or symptomatic arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months prior to first dose with study drug
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine
  • Child-Pugh B cirrhosis (or worse) or a history of hepatic encephalopathy
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study
  • Major surgery or a wound that has not fully healed within 4 weeks of enrollment
  • Patients who need anticancer chemotherapy other than the study drugs during the study or within 4 weeks of study enrollment. Anti-cancer therapy is defined as any agent or combination of agents with clinically proven anti-tumor activity administered by any route with the purpose of affecting the malignancy, either directly or indirectly, including palliative and therapeutic endpoints
  • Patients who need anti-cancer hormonal therapy during the study or within 2 weeks of first study enrollment
  • Patients who need radiotherapy to target lesions during study or within 2 weeks of enrollment
  • Patients who had bone marrow transplant or stem cell rescue
  • Patients who need investigational drug therapy outside of this trial during or within 4 weeks of first study treatment

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE
Contact: Dae Won Kim
Phone: 813-745-6898

PRIMARY OBJECTIVE:

I. To determine the 6 month overall survival in patients with advanced, refractory gastric and gastroesophageal junction (GEJ) adenocarcinoma receiving trifluridine and tipiracil hydrochloride (TAS 102) in combination with ramucirumab.

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events and tolerability of TAS 102 plus ramucirumab in patients with advanced, refractory gastric and GEJ adenocarcinoma.

II. To determine the efficacy of TAS 102 in combination with ramucirumab based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

III. To determine the progression free survival in patients with advanced, refractory gastric and GEJ adenocarcinoma receiving TAS 102 in combination with ramucirumab.

OUTLINE:

Patients receive TAS 102 orally (PO) twice daily (BID) on days 1-5 and 8-12 and ramucirumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 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 12 weeks for 6 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Moffitt Cancer Center

Principal Investigator
Dae Won Kim

  • Primary ID MCC-19477
  • Secondary IDs NCI-2018-03261
  • Clinicaltrials.gov ID NCT03686488