The ongoing study is a Phase II, open-label study to evaluate the efficacy of MBP-426 at a dose of 170 mg/m2 in combination therapy in patients with second line metastatic gastric, gastro-esophageal junction or esophageal adenocarcinoma.

This study will start with a Phase Ib portion, at a dose of 226 mg/m2, a dose in which good tolerability was demonstrated in the Phase I trial. A cohort may be enrolled at 301 mg/m2, if 226 mg/m2 is well tolerated. The dose determined from the Phase Ib portion of the study will then be evaluated in the Phase II portion.

This design will permit evaluation of a true positive or negative response while limiting over exposure of patients to the study drug. If this regimen does offer a positive response, its reduced toxicity and potentially greater efficacy may yield better outcomes for patients requiring second-line therapy for UGI cancer.

Following completion of the Phase Ib part of the present trial, the dose recommended for use in the Phase II part is 170 mg/m2 MBP-426.

Inclusion Criteria:

Phase Ib:

1. Advanced or metastatic solid tumor malignancy that is refractory to STD therapy, or that has relapsed after STD therapy, or for which conventional therapy is not reliably effective, or no effective therapy is available.

2. Measurable disease as defined by RECIST. If recurrence is documented following radiation therapy, the recurrence must have occurred outside the radiation field. Lesions which are located within a previously irradiated field are not considered measurable.

3. Age ≥18.

4. ECOG performance status: 0, 1 or 2.

5. Adequate organ and system function:

   • Bone marrow: ANC ≥1500/mm3, platelet count ≥100000/mm3, and Hb ≥9 g/dL;
   • Coagulation: PT <1.3 x ULN, PTT >LLN, <1.1 x ULN
   • Renal: Serum creatinine of ≤1.5 x the institution's ULN or calculated creatinine clearance ≥60 mL/min/1.73m2;
   • Hepatic: Total bilirubin ≤1.5 mg/dL, ALT and AST ≤2.5 x ULN (or 5 x ULN), and ALP ≤2.5 x ULN (or 5 x ULN).

6. Recovered to ≤Gr 1 from all acute toxicities caused by prior cancer therapies except for residual toxicities which do not pose an ongoing medical risk.

7. If of childbearing potential, agree to use an effective method of contraception prior to study entry, for the duration of the study, and for 30 days after the last dose of MBP-426 with FA/5-FU. A negative pregnancy test must be documented at baseline. Patients may not breastfeed while in this study.

8. Have the ability to maintain a central IV access.

9. Able to comply with the protocol treatments and procedures.

10. Provide written informed consent indicating that they are aware of the investigational nature of this study and in keeping with the institution's policies.

Phase II:

1. Inoperable, histologically, or cytologically confirmed, locally advanced or metastatic gastric, GE junction, or esophageal adenocarcinoma that has recurred or progressed following 1 prior chemotherapy.
2. Measurable disease as defined by RECIST. If recurrence is documented following radiation therapy, the recurrence must have occurred outside the radiation field. Lesions which are located within a previously irradiated field are not considered measurable.
3. ECOG performance status: 0 or 1.
4. Identical to criteria numbers 3-10 for Phase Ib portion of the study.

Exclusion Criteria (Phase Ib and II):

1. Major surgery within 14 days prior to study enrollment.
2. Radiotherapy, hormonal therapy, immunotherapy, or investigational agents within 30 days of enrollment (6 weeks for mitomycin C). A washout is required for chemotherapy, antibodies and small molecules, equivalent to at least 5 half-lives or 30 days, whichever is shorter, prior to study entry. Concurrent use of bisphosphonates is permitted.
3. Have had a past or have a current 2nd primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin, or other malignancy treated at least 3 years previously with surgery and/or radiotherapy and no evidence of recurrence since that time).
4. Known or clinical evidence of CNS metastases.
5. Receiving high-dose steroids more than a dexamethasone-equivalent dose of 4 mg/day.
6. Current active infections requiring anti-infectious treatment.
7. Significant intercurrent illnesses that would have compromise the safety of the patient or compromise the ability of the patient to complete the study.
8. Documented or known hematologic malignancy and/or bleeding disorder.
9. Peripheral neuropathy ≥Gr 2 (NCI-CTCAE, Ver. 3.0).
10. Any requirement(s) for therapeutic anticoagulation that increases INR or aPTT above the normal range (low dose DVT or line prophylaxis is allowed).
11. Have NYHA Class 3 or 4 heart disease, active ischemia, or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy.
12. History of allergy to any of the treatment components (oxaliplatin, 5-FU, FA, liposome, ferritin).