A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers
Condition: GastroEsophageal Cancer
Intervention: Irinotecan; Oxaliplatin; Leucovorin; 5-Fluorouracil; Paclitaxel; Radiation Therapy; Carboplatin
Intervention description: May help shrink tumor before surgery.; May help shrink tumor before surgery.; May help shrink tumor before surgery.; May help shrink tumor before surgery.; Paclitaxel may stop cancer cells from growing and spreading.; May help shrink tumor.; Carboplatin may stop cancer cells from growing.
Intervention MeSH terms: Leucovorin; Paclitaxel; Carboplatin; Fluorouracil; Oxaliplatin; Irinotecan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GastroEsophageal Cancer

Summary:

      This research study is studying a combination of interventions as a possible treatment for
      gastroesophageal (GE) junction cancer.

      The interventions involved in this study are:

      -FOLFIRINOX which is made up of 4 different drugs:

        -  5-Fluorouracil (5-FU)

        -  Oxaliplatin

        -  Irinotecan

        -  Leucovorin

        -  Paclitaxel

        -  Carboplatin

        -  Proton Beam Radiation Therapy
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed T 3/4 or N+ (> 1 cm in size or FDG avid)
             gastric or gastroesophageal (GE) junction cancer. Diagnosis must be confirmed by the
             Mass General Hospital pathology department.

          -  Age 18 years or older. There will be no upper age restriction.

          -  ECOG performance status ≤ 1

          -  Life expectancy of greater than 3 months

          -  Participants must have adequate organ and marrow function as defined below:

               -  absolute neutrophil count ≥ 1,500 cells/mm3

               -  platelets ≥ 75,000 cells/mm3

               -  total bilirubin ≤ 1.5 x upper limit of normal, or, for patients who have

               -  undergone biliary stenting, total bilirubin of ≤ 2 or two down trending values.

               -  AST(SGOT) ≤ 2.5 × upper limit of normal

               -  ALT (SGPT) ≤ 2.5 x upper limit of normal

               -  creatinine ≤ 1.5 mg/dL, or

               -  creatinine clearance ≥ 30 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  The effects of both radiation therapy and the chemotherapy agents used in this trial
             are known to be teratogenic. Therefore, women of child-bearing potential and men must
             agree to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation plus 30
             days from the last date of study drug administration. Should a woman become pregnant
             or suspect she is pregnant while she or her partner is participating in this study,
             she should inform her treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Evidence of metastatic disease as determined by chest CT scan, abdomen/pelvis CT scan
             (or MRI with gadolinium and/or manganese) within six weeks of study entry. Distant
             nodal disease is allowed if it is in the radiation port.

          -  Any prior chemotherapy, targeted/biologic therapy, or radiation for treatment of the
             participant's gastric or GE junction cancer.

          -  Receipt of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) prior to entering the study or those who have not recovered from adverse
             events due to agents administered more than 4 weeks earlier.

          -  Treatment of other invasive carcinomas within the last five years with greater than 5%
             risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell
             carcinoma/ squamous cell carcinoma of the skin are allowed.

          -  Receipt of any other investigational agents within 4 weeks preceding the start of
             study treatment.

          -  Serious concomitant systemic disorders incompatible with the study (at the discretion
             of the investigator), such as significant cardiac or pulmonary morbidity (e.g.
             congestive heart failure, symptomatic coronary artery disease and/or cardiac
             arrhythmias not well controlled with medication) or myocardial infarction within the
             last 12 months, or ongoing infection as manifested by fever.

          -  History of uncontrolled seizures, central nervous system disorders or psychiatric
             disability judged by the investigator to be clinically significant, precluding
             informed consent, or interfering with compliance or drug intake.

          -  Pregnant women are excluded from this study because radiation therapy and the
             chemotherapy agents to be used have the potential for teratogenic or abortifacient
             effects. Because there is an unknown but potential risk for adverse events in nursing
             infants secondary to treatment of the mother with these agents, breastfeeding should
             be discontinued while the mother is receiving protocol therapy.

          -  Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment,
             without complete recovery.

          -  No concurrent administration of cimetidine (as it can decrease the clearance of 5-FU).
             Another H2-blocker or proton pump inhibitor may be substituted before study entry.

          -  Known, existing uncontrolled coagulopathy.

          -  Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and at
             least six months earlier). Prior topical fluoropyrimidine use is allowed.

          -  Known hypersensitivity to 5-fluorouracil or known DPD deficiency.

          -  History of allergic reaction(s) attributed to compounds of similar chemical or
             biologic composition to 5-fluorouracil, irinotecan, or oxaliplatin