FOLFOX-A in the Treatment of Metastatic or Advanced Unresectable Gastric, Gastro-Esophageal Junction Adenocarcinoma
Condition: Gastro-Esophageal Junction Adenocarcinoma; Gastric Cancer
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: Nab-paclitaxel 150 mg/m^2; Oxaliplatin 85 mg/m^2; 5-FU 1200 mg/m^2 x 2 D; Leucovorin 400 mg/m^2
Intervention description: Stage I (N=12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15; Stage I (N= 12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15; Stage I (N= 12), on day 1 and day 15-16 Stage II (N= 25),on day 1 and day 15-16; Stage I (N= 12),on day 1 and day 15 Stage II (N= 25), on day 1 and day 15
Intervention MeSH terms: Leucovorin; Paclitaxel; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Open-Label
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: FOLFOX; Nab-Paclitaxel

Summary:

      This is an open label, single-arm phase II, multi-institutional trial to evaluate the
      efficacy and safety of the combination of nab-paclitaxel and FOLFOX (FOLFOX-A) as first line
      therapy for patients diagnosed with histologically-confirmed advanced gastric/GEJ
      adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

        Subject must meet all of the following applicable inclusion criteria to participate in this
        study:

          -  Written informed consent and HIPAA authorization for release of personal health
             information. NOTE: HIPAA authorization may be included in the informed consent or
             obtained separately.

          -  Age ≥ 18 years at the time of consent.

          -  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.

          -  Prior neoadjuvant or adjuvant chemotherapy, hormonal therapy, immunotherapy, radiation
             or chemoradiotherapy must have been completed at least 6 months prior to documented
             recurrence or metastatic disease. NOTE: patients must not have received previous
             systemic treatment for metastatic disease.

          -  Evaluable disease according to RECIST v1.1 for solid tumors, within 28 days prior to
             registration.

          -  Demonstrate adequate organ function as described below; all screening labs to be
             obtained within 28 days prior to registration.

               -  Bilirubin < 1.5 mg/dL

               -  Patients must have adequate liver function: AST and ALT < 2.5 x upper limit of
                  normal, alkaline phosphatase < 2.5 x upper limit of normal, unless bone or liver
                  metastasis is present (≤5 x upper limit of normal).

               -  Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3
                  (transfusion independent, defined as not receiving platelet transfusions within 7
                  days prior to laboratory sample), Hemoglobin > 9.0g/dL and ANC > 1,500 cells/mm3.

               -  Patients must have adequate renal function: creatinine <1.5 mg/dL or creatinine
                  clearance ≥60mL/min is recommended; however, institutional norms are acceptable.

          -  Females of child-bearing potential (defined as a sexually mature woman who (1) has not
             undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy
             [the surgical removal of both ovaries] or (2) 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
                  investigational product (IP), and while on study medication (including dose
                  interruptions) and for 30 days following the last dose of IP; and

               -  Have a negative serum pregnancy test (β -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].

        Exclusion Criteria

        Subjects meeting any of the criteria below may not participate in the study:

          -  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.

          -  History of slowly progressive dyspnea and unproductive cough, or pulmonary conditions
             such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, hypersensitivity
             pneumonitis or multiple allergies. See section 6.5.1.

          -  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