A Phase Ib/II Study of MBP-426 in Patients with Second Line Gastric, Gastro-Esophageal, or Esophageal Adenocarcinoma (MBP-426 201)
The goal of the Phase 1b portion of this clinical research study is to find the highest tolerable dose of MBP-426 that can be given in combination with leucovorin and 5-fluorouracil (5-FU) to patients with advanced or metastatic solid tumors. The safety of this drug combination will also be studied.
Disease Group: Gastrointestine
Treatment Agent: 5-FU
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: NA
Sponsor: Mebiopharm Co., Ltd.
Return Visit: Once every week
Home Care: NA
Primary Objectives Phase Ib: 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 5-FU. This stage is open to patients with advanced or metastatic solid tumors. Phase II: Phase II: To evaluate the efficacy of the combination therapy at the Phase II MBP-426 dose (determined to be 170 mg/m2) in patients with second line metastatic gastric, gastro-esophageal junction, or esophageal adenocarcinoma. Secondary Objectives Phase Ib: · To characterize the safety profile of the combination therapy · To undertake a preliminary exploration of anti-tumor activity of the combination therapy · To determine the plasma and urine pharmacokinetics of MBP-426 Phase II: · To characterize the safety profile of the combination therapy
IRB Review and Approval Date: 12/15/2009
Recruitment Status: Not Accepting
Projected Accrual: 62
1) For Phase Ib: 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) For Phase Ib: 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) For Phase Ib: Age 18 years or older.
4) For Phase Ib: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5) For Phase Ib: Adequate organ and system function defined by the following parameters: a. Bone marrow: Absolute neutrophil count (ANC) of =/>1500/mm^3, platelet count =/>100,000/mm^3, and hemoglobin =/>9 g/dL; b. Coagulation: PT <1.3 x ULN, PTT >LLN, <1.1 x ULN; c. Renal: Serum creatinine of =/<1.5 x the institution’s upper limit of normal (ULN) or calculated creatinine clearance =/>60 mL/min/1.73m^2;
6) (Continuaton of criteria # 5) or d. Hepatic: Total bilirubin =/<1.5 mg/dL, and alanine aminotransferase (ALT) or 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)
7) For Phase Ib: 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.
8) For Phase Ib: 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 infants while in this study.
9) For Phase Ib: Have the ability to maintain a central IV access (e.g., PICC, Groshong, or Hickman line).
10) For Phase Ib: Able to comply with the protocol treatments and procedures.
11) For Phase Ib: 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.
12) For Phase II: 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.
13) For Phase II: 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.
14) ECOG performance status of 0 or 1.
15) For Phase II: Identical to criteria numbers 3-11 for Phase Ib portion of the study.
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 5 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.
12) History of allergy to any of the treatment components (oxaliplatin, 5-FU, folinic acid, liposome, ferritin).