Study of MBP-426 in Patients With Second Line Gastric, Gastroesophageal, or Esophageal Adenocarcinoma

• To determine the dose of MBP-426 for use in the Phase II portion of this study of MBP-426 administered every 21 days in combination with leucovorin (folinic acid or FA) and fluorouracil (5-FU) [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
• To evaluate the efficacy of the combination therapy at the Phase II MBP-426 dose in patients with second line metastatic gastric, gastro esophageal junction, or esophageal adenocarcinoma. [ Time Frame: 16 months ] [ Designated as safety issue: No ]

• To characterize the safety profile of the combination therapy [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
• To determine the plasma and urine pharmacokinetics of MBP-426 when given in combination with leucovorin and 5-FU [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• To undertake a preliminary exploration of anti-tumor activity of the combination therapy [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• To characterize the safety profile of the combination therapy [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]

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.

• Gastric Adenocarcinoma
• Gastroesophageal Adenocarcinoma
• Esophageal Adenocarcinoma

Inclusion Criteria:

Phase Ib:

1. Advanced or metastatic solid tumor malignancy that is refractory to standard therapy, or that has relapsed after standard 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 years or older.
4. ECOG performance status of 0, 1 or 2.

5. Adequate organ and system function defined by the following parameters:

   • Bone marrow: Absolute neutrophil count (ANC) of >=1500/mm3, platelet count >=100,000/mm3, and hemoglobin >=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 upper limit of normal (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 in the case of liver metastases), and alkaline phosphatase <=2.5 x ULN (or 5 x ULN in the case of liver metastases).
6. Recovered to <=Grade 1 from all acute toxicities caused by prior cancer therapies except for residual toxicities, such as alopecia, 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 (in combination with FA/5-FU). A negative serum or urine pregnancy test must be documented at baseline for women of childbearing potential. 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 policies of the institution.

Phase II:

1. Inoperable, histologically, or cytologically confirmed, locally advanced or metastatic gastric, gastro-esophageal 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 of 0 or 1.
4. Identical to criteria numbers 3-10 for Phase Ib portion of the study.

Exclusion Criteria:

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 period 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 second 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 per day).
6. Current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals).
7. Significant intercurrent illnesses that, in the opinion of the Investigator, 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 >= grade 2 (NCI-CTCAE, Version 3.0).
10. Any requirement(s) for therapeutic anticoagulation that increases INR or aPTT above the normal range (low dose deep vein thrombosis [DVT] or line prophylaxis is allowed).
11. Have New York Heart Association (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 including angina pectoris, cardiac arrhythmia, hypertension, or congestive heart failure.
12. History of allergy to any of the treatment components (oxaliplatin, 5-FU, folinic acid, liposome, ferritin).