Combination Chemotherapy and Nab-Paclitaxel in Treating Patients with Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; NOTE: HIPAA authorization may be included in the informed consent or obtained separately
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 28 days prior to registration
- Histologically-confirmed advanced or metastatic unresectable gastric carcinoma, or adenocarcinoma of the gastroesophageal junction
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 for solid tumors, within 28 days prior to registration
- Obtained within 28 days prior to registration: Bilirubin =< 1.5 mg/dL
- Obtained within 28 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal, unless bone or liver metastasis is present (=< 5 x upper limit of normal)
- Obtained within 28 days prior to registration: Alkaline phosphatase =< 2.5 x upper limit of normal, unless bone or liver metastasis is present (=< 5 x upper limit of normal)
- Obtained within 28 days prior to registration: Platelets > 100,000 cells/mm^3 (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample)
- Obtained within 28 days prior to registration: Hemoglobin > 9.0 g/dL
- Obtained within 28 days prior to registration: Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Obtained within 28 days prior to registration: Creatinine =< 1.5 mg/dL or creatinine clearance >= 60 mL/min is recommended; however, institutional norms are acceptable
- Females of child-bearing potential (defined as a sexually mature woman who  has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or  has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must: * Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use and be able to comply with effective contraception without interruption 28 days prior to starting investigation product (IP) therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and * Have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) result at screening and agree to ongoing pregnancy testing prior to each treatment and after the end of study therapy; this applies even if the subject practices true abstinence from heterosexual contact * Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy * NOTE: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Prior systemic treatment
- Her-2 positive gastric tumor
- Treatment with any investigational products within 28 days prior to study registration
- Preexisting peripheral neuropathy is not allowed from any cause
- Known history of human immunodeficiency virus (HIV) or hepatitis C (baseline testing is not required)
- Patients with active sepsis or pneumonitis
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to trial registration and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial registration
- Known hypersensitivity to fluorouracil (5-FU), oxaliplatin, or other platinum agents
- Known hypersensitivity to nab-paclitaxel or any of its excipients
- Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not required)
- Ongoing or active infection requiring systemic treatment (must be afebrile for >= 48 hours prior to study registration)
- Uncontrolled intercurrent illness including, but not limited to any of the following: * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
- Known additional malignancy within the past 3 years; exceptions include treated localized basal cell or squamous cell carcinoma of the skin, in situ cervical or vulvar carcinoma that has undergone potentially curative therapy, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer (Gleason sore 6); any cancer curatively treated > 3 years prior to registration with no clinical evidence of recurrence is permitted
- Psychiatric illness/social situations that would limit compliance with study requirements
- Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints
I. To estimate the overall objective response rate (complete response [CR]+partial response [PR]) of leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) combined with nab-paclitaxel (FOLFOX-A) in patients with advanced gastric, gastroesophageal junction adenocarcinoma.
I. To evaluate clinical efficacy by assessment of median overall survival (OS), progression-free survival (PFS), time to progression (TTP) as well as best overall response rate (ORR) and disease control rate (DCR).
II. Describe the safety and toxicity profile of the combination of nab-paclitaxel and FOLFOX in this population.
Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on days 1 and 14, and fluorouracil IV continuously over 46-48 hours on days 1-2 and 14-15. Courses 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 3 months for up to 2 years.
Trial Phase Phase II
Trial Type Treatment
Al Bowen Benson III
- Primary ID BTCRC GI15-015
- Secondary IDs NCI-2017-01762, STU00205558
- Clinicaltrials.gov ID NCT03283761