Ramucirumab Plus Trifluridine/Tipiracil (TAS-102) for Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: An Investigator-Initiated, Randomized Non-Inferiority Phase 2 Study
Overview
- Phase
- Phase 2
- Intervention
- Quality-of-Life Assessment
- Conditions
- Clinical Stage III Gastric Cancer AJCC v8
- Sponsor
- Academic and Community Cancer Research United
- Enrollment
- 116
- Locations
- 15
- Primary Endpoint
- Progression-free survival
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.
Detailed Description
PRIMARY OBJECTIVE: I. 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 trifluridine and tipiracil hydrochloride (TAS-102) versus (vs.) paclitaxel and ramucirumab. SECONDARY OBJECTIVES: I. To assess overall survival (OS) in this patient population for each regimen. II. Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire for each regimen. III. To determine the safety of the combination of ramucirumab with TAS-102 in this patient population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive TAS-102 orally (PO) twice daily (BID) on days 1-5 and 8-12, and ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30-35 days, then every 3 months for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 Response Evaluation Criteria in Solid Tumors (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
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Ability to swallow oral medications
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 gastrointestinal (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
Arms & Interventions
Arm A (TAS-102, ramucirumab)
Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm A (TAS-102, ramucirumab)
Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Ramucirumab
Arm A (TAS-102, ramucirumab)
Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Trifluridine and Tipiracil Hydrochloride
Arm B (paclitaxel, ramucirumab)
Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm B (paclitaxel, ramucirumab)
Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm B (paclitaxel, ramucirumab)
Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Ramucirumab
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: Up to 1 year
Progression free survival is defined as the time interval between randomization date and the date of disease progression or death (referred to as an "event"), whichever occurs first. Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median progression free survival will be estimated using the Kaplan-Meier method for each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.
Secondary Outcomes
- Overall survival (OS)(Up to 3 years)
- Quality of life (QOL)(Up to 3 years)
- Incidence of adverse events(Up to 3 years)