This will be a Phase Ib/II, open-label, non-randomized, single arm study of MBP-426. MBP-426
will be administered every 21 days as an intravenous (IV) infusion at a starting dose of 226
mg/m2, in combination with leucovorin (folinic acid or FA) and 5 fluorouracil (FU).
Following MBP-426 administration, leucovorin (400 mg/m2) will be administered IV with an IV
bolus of 400 mg/m2 fluorouracil (on the same day as MBP 426), followed by 2400 mg/m2
fluorouracil continuous IV (CIV) infusion over 46 hours. Patients will be premedicated 15
minutes prior to MBP-426 infusion with 10 mg dexamethasone (IV), 8 mg Zofran®, and 25 mg
Benadryl®.
In the Phase Ib portion of this study, the first cohort of patients will receive MBP-426 at
a dose of 226 mg/m2. Subsequent patients will be treated at doses in accordance with the
table below. The dose for the Phase II study will be determined based on the toxicity seen
in the Phase Ib patients.
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. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. (See
Appendix I.)
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, alanine aminotransferase (ALT) and
aspartate transaminase (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 (e. g., PICC, Groshong, or Hickman
line).
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. Identical to criteria numbers 3-10 for Phase Ib portion of the study.
Exclusion Criteria:
1. Radiotherapy or major surgery within 14 days prior to study enrollment.
2. Anticancer therapy (chemotherapy, radiotherapy, hormonal therapy, immunotherapy, or
investigational agents) within 30 days of enrollment (6 weeks for mitomycin C).
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 central nervous system (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
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 international
normalized ratio (INR) or activated partial thromboplastin time (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. (See
Appendix II).
12. History of allergy to any of the treatment components (oxaliplatin, 5-FU, folinic
acid, liposome, ferritin).
