IRB Study Number FLA21-052
Status Recruiting
Phase Phase 2
Institute Taussig Cancer Institute
Description
Primary Objective
2.11 To compare, in a non-inferiority fashion, the progression-free survival (PFS) in patients with metastatic refractory gastric/GEJ adenocarcinoma receiving the combination of ramucirumab with TAS-102 vs. paclitaxel and ramucirumab.
Secondary Objectives
2.21 To assess overall survival (OS) in this patient population for each regimen.
2.22 Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire for each regimen.
2.23 To determine the safety of the combination of ramucirumab with TAS-102 in this patient population.
Inclusion Criteria
3.11 Age ≥ 18 years.
3.12 Histological or cytological confirmation of adenocarcinoma of the stomach or gastroesophageal junction.
3.13 Have locally advanced unresectable or metastatic disease that has progressed ≤ 180 days since last treatment.
3.14 One or more measurable or nonmeasurable evaluable lesions per RECIST as defined in Section 11.0.
3.15 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.
3.16 ECOG Performance Status (PS) 0 or 1. (Form is available on the ACCRU web site)
3.17 Ability to swallow oral medications.
3.18 The following laboratory values obtained ≤7 days prior to registration.
• Absolute neutrophil count (ANC) ≥1500/mm3
• Platelet count ≥100,000/mm3
• 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 x ULN, 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) ≥50 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).
3.19 Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
3.19a Ability to complete questionnaire(s) by themselves or with assistance.
3.19b Provide informed written consent ≤28 days prior to registration.
3.19c Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
3.19d 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
3.21 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
3.22 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.
3.23 Previous treatment with TAS-102 or ramucirumab
3.24 Previous taxane therapy ≤180 days prior to registration
3.25 Any grade 3-4 GI bleeding ≤90 days prior to registration
3.26 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.
3.27 Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, ≤180 days prior to registration.
3.28 Prior history of GI perforation/fistula ≤180 days of registration or risk factors for perforation.
3.29a Serious or nonhealing wound, ulcer, or bone fracture ≤ 28 days prior to registration.
3.29b Major surgery ≤28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement ≤7 days prior to registration.
3.29c Elective or planned major surgery to be performed during the course of the clinical trial.
3.29d 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.
3.29e Uncontrolled or poorly-controlled hypertension (≥150 mmHg systolic or ≥90 mmHg diastolic for ≥4 weeks) despite standard medical management.
3.29f 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.
3.29g 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.
3.29h Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
3.29i 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.
3.29j Receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. NOTE: Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
