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An Open-Label, Multicenter, Randomized Phase Ib/II Study of FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

An Open-Label, Multicenter, Randomized Phase Ib/II Study of FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer

This open-label, multicenter, randomized study will consist of a Phase Ib portion: a safety
run-in period with 3 ascending doses of E7820; and a Phase II portion: a randomized 3-arm
design. Approximately 135 patients with measurable, nonresectable locally advanced or
metastatic colorectal adenocarcinoma, who have failed first-line chemotherapy, will be
enrolled in the study (approximately 15 patients in the Phase Ib portion and 120 patients in
the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II
portion of the study. Patients will receive up to a planned total of 6 cycles of study
treatment unless there is occurrence of progressive disease, unacceptable toxicity,
withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death,
whichever occurs first. After 6 cycles, patients in Arm 3 (FOLFIRI + E7820) who demonstrate
clinical benefit may continue single agent E7820 for long as clinical benefit is sustained
and the treatment is well tolerated. If the treating physician does not feel comfortable
discontinuing chemotherapy after 6 cycles, further chemotherapy may be considered following
discussion with the medical monitor and sponsor.

Inclusion Criteria:

Patients may be entered in the study only if they meet all of the following criteria:

1. Male or female patient greater than or equal to 18 years of age;

2. Histologically or cytologically confirmed nonresectable locally advanced or
metastatic colorectal adenocarcinoma;

3. Patients must have failed a first-line chemotherapy regimen for nonresectable locally
advanced or mCRC (first-line bevacizumab is allowed). Patients randomized to the
Phase Ib portion can have up to 3 total prior regimens (including adjuvant therapy in
addition to treatment for advanced disease);

4. At least 1 site of measurable disease by the Response Evaluation Criteria in Solid
Tumors (RECIST version 1.1) criteria;

5. Life expectancy of > 3 months;

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1;

7. Patients must have adequate renal function as evidenced by serum creatinine <2 mg/dL
and creatinine clearance >50 mL/minute per the Cockcroft and Gault formula;

8. Patients must have adequate bone marrow function as evidenced by absolute neutrophil
count (ANC) >1.5 x 109/L, platelets >100 x 109/L, hemoglobin >9.0 g/dL (a hemoglobin
<9.0 g/dL at Screening is acceptable if it is corrected to >9 g/dL by growth factor
or transfusion prior to first dose);

9. Patients must have adequate liver function as evidenced by bilirubin <1.5 times the
upper limit of the normal range (ULN), and alkaline phosphatase, alanine
aminotransferase (ALT), and aspartate aminotransferase (AST) <3 X ULN (in the case of
liver metastases, <5 X ULN). If there are bone metastases, liver-specific alkaline
phosphatase may be separated from the total and used to assess liver function instead
of total alkaline phosphatase;

10. Blood pressure must be well-controlled (<140/90 mmHg at screening) with or without
antihypertensive medication. Patients must have no history of hypertensive crisis or
hypertensive encephalopathy;

11. Male or female patients of child-producing potential must agree to use double barrier
contraception, oral contraceptives, or avoidance of pregnancy measures during the
study and for 90 days after the last day of treatment;

12. Females of childbearing potential must have a negative serum pregnancy test;

13. Females may not be breastfeeding; and

14. Ability to understand and willingness to sign a written consent.

Exclusion Criteria:

Patients will not be entered in the study for any of the following reasons:

1. Received chemotherapy, targeted therapy, radiotherapy, surgery, immunotherapy, or
treatment in another clinical study within the 30 days prior to commencing study
treatment or have not recovered from side effects of all treatment-related toxicities
to Grade <1, except for peripheral neuropathy (Grade 1 and Grade 2 are permitted) and

2. Previously received irinotecan or irinotecan derivatives;

3. Previously received anti-alpha 2 integrin therapy;

4. History of other malignancies except: (1) adequately treated basal or squamous cell
carcinoma of the skin; (2) curatively treated, a) in situ carcinoma of the uterine
cervix, b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively
treated solid tumor with no evidence of disease for >5 years;

5. Presence of brain metastases, unless the patient has received adequate treatment at
least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids
for at least 4 weeks prior to randomization;

6. Are currently receiving any other anticancer treatment;

7. Palliative radiotherapy is not permitted throughout the study period;

8. Serious non-healing wound, ulcer, or active bone fracture;

9. Major surgical procedure, open biopsy or significant traumatic injury within 28 days
prior to Day 1, or anticipation of need for a major surgical procedure during the
course of the study;

10. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any
other medical condition that would preclude adequate absorption or result in the
inability to take oral medication;

11. Significant cardiovascular impairment (history of congestive heart failure New York
Heart Association [NYHA] Grade >2, unstable angina or myocardial infarction within
the past 6 months, or serious cardiac arrhythmia);

12. Active hemoptysis (defined as bright red blood of

13. Current or recent use (within 7 days) of full-dose warfarin (except low-dose warfarin
as required to maintain patency of preexisting, permanent indwelling IV catheters).
For subjects receiving warfarin, International Normalization Ratio (INR) should be
<1.5. Patients may have prophylactic use of low molecular weight heparin, however
therapeutic use of heparin or low molecular weight heparin is not acceptable;

14. History of bleeding diathesis or coagulopathy;

15. Any history of cerebral vascular accident, transient ischemic attack or ≥ Grade 2
peripheral vascular disease, unless they have had no evidence of active disease for
at least 6 months prior to randomization;

16. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6
months prior to Day 1, unless affected area has been removed surgically;

17. Patients with organ allografts requiring immunosuppression;

18. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen,
or active hepatitis C positive;

19. Patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin;

20. Hypersensitivity to sulfonamide derivatives; or

21. Have any medical condition that would interfere with the conduct of the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety Parameter: Adverse Events

Outcome Description:

Phase 1B: To determine the MTD of E7820 in combination with FOLFIRI as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7820. Phase II: Safety and tolerability of E7820 at the MTD determined in Phase Ib in combination with FOLFIRI as measured by rate of adverse events by body system and grade.

Outcome Time Frame:

Until study termination; 3 years

Safety Issue:


Principal Investigator

Harish Dave

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

January 2011

Related Keywords:

  • Colorectal Cancer
  • Colorectal Neoplasms



Northwest Medical Specialties, PLLCTacoma, Washington  98405
University of Texas Southwestern Medical CenterDallas, Texas  
Rocky Mountain Cancer Center - MidtownDenver, Colorado  80218
University of North Carolina at Chapel HillChapel Hill, North Carolina  27599
Summit Medical GroupSummit, New Jersey  07901
Hematology Oncology Associates SJ P.A.Mount Holly, New Jersey  08060