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Study of MBP-426 in Patients With Second Line Gastric, Gastroesophageal, or Esophageal Adenocarcinoma
This study is currently recruiting participants.
Verified by Mebiopharm Co., Ltd, August 2009
First Received: August 17, 2009   Last Updated: August 20, 2009   History of Changes
Sponsor: Mebiopharm Co., Ltd
Collaborator: AAIPharma
Information provided by: Mebiopharm Co., Ltd
ClinicalTrials.gov Identifier: NCT00964080
  Purpose

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.


Condition Intervention Phase
Gastric Adenocarcinoma
Gastroesophageal Adenocarcinoma
Esophageal Adenocarcinoma
Drug: MBP426/Leucovorin/5-FU
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase Ib/II Study of MBP-426 in Patients With Second Line Gastric, Gastro Esophageal, or Esophageal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Mebiopharm Co., Ltd:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 62
Study Start Date: May 2009
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
MBP426/Leucovorin/5-FU: Experimental

MBP-426 infusion rate will start at 75 mL/hr for 15 minutes, will increase to 100 mL/hr for the next 15 minutes, and then increase to a maximum of 150 mL/hr for the remainder of the study drug administration, as tolerated.

Leucovorin is to be administered at a dose of 400 mg/m² as a 2-hour infusion on Day 1, repeated every 3 weeks. Leucovorin administration will be administered immediately after the MBP-426 infusion, in the absence of allergy/infusion reaction. Leucovorin will be administered concurrently with 5-FU administration.

5-FU is administered as a bolus of 400 mg/m² over 5-15 minutes, beginning concurrently with the leucovorin infusion, after the MBP-426 administration on Day 1. This is followed by a 46-hour continuous infusion of 2400 mg/m² 5-FU. These infusions (bolus and continuous) are to be repeated every 3 weeks.

Drug: MBP426/Leucovorin/5-FU

MBP-426 (30 mL vials, 24 mg of MBP-426). MBP-426 infusion rate will start at 75 mL/hr for 15 minutes, will increase to 100 mL/hr for the next 15 minutes, and then increase to a maximum of 150 mL/hr for the remainder of the study drug administration.

Leucovorin is to be administered at a dose of 400 mg/m² as a 2-hour infusion on Day 1, repeated every 3 weeks. Leucovorin administration will be administered immediately after the MBP-426 infusion, in the absence of allergy/infusion reaction. Leucovorin will be administered concurrently with 5-FU administration.

5-FU is administered as a bolus of 400 mg/m² over 5-15 minutes, beginning concurrently with the leucovorin infusion, after the MBP-426 administration on Day 1. This is followed by a 46-hour continuous infusion of 2400 mg/m² 5-FU. These infusions (bolus and continuous) are to be repeated every 3 weeks.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00964080

Locations
United States, Texas
Mary Crowley Medical Research Center Recruiting
Dallas, Texas, United States, 76201
Contact: Neil Senzer, MD     214-658-1952     nsenzer@marycrowley.org    
Contact: Alyssa Roth     972-566-3061     aroth@marycrowley.org    
Principal Investigator: Neil N Senzer, MD            
Sponsors and Collaborators
Mebiopharm Co., Ltd
AAIPharma
  More Information

No publications provided

Responsible Party: Mebiopharm Co., Ltd. ( Nobuyuki Yamagata/ Project Management & Business Development Dept. )
Study ID Numbers: MBP-426 201
Study First Received: August 17, 2009
Last Updated: August 20, 2009
ClinicalTrials.gov Identifier: NCT00964080     History of Changes
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Vitamin B Complex
Neoplasms by Histologic Type
Digestive System Neoplasms
Gastrointestinal Diseases
Growth Substances
Physiological Effects of Drugs
Leucovorin
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Neoplasms by Site
Stomach Diseases
Vitamins
Stomach Neoplasms
Gastrointestinal Neoplasms
Micronutrients
Esophageal Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 04, 2010