FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer

NCT ID: NCT01133990

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-04
• Study Completion Date: 2011-02-18

Brief Summary

The purpose of the Phase Ib portion is to find out the highest dose of study drug that can safely be given when tested in a small group of subjects.

The purpose of the Phase II portion is to find out how safe the study drug is when taken at the highest dose in a larger group of subjects.

Detailed Description

The primary purpose for Phase 1b: to determine the maximum tolerated dose (MTD) of E7820 recommended for Phase 2 when administered in combination with the FOLFIRI regimen (irinotecan, leucovorin, and 5-fluorouracil [5-FU]) in participants with locally advanced or metastatic colorectal cancer (mCRC) who have failed first-line therapy. Phase 2: to evaluate the safety and tolerability of E7820 administered in combination with the FOLFIRI regimen, compared with FOLFIRI alone and FOLFIRI plus bevacizumab, in patients with locally advanced or mCRC who have failed first-line therapy.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFIRI

The FOLFIRI regimen consists of irinotecan at 180 mg/m2 (IV infusion) on Day 1 and Day 15 of each 28-day cycle, leucovorin at 200 mg/m2 (400 mg/m2 if using d,l-racemic mixture of leucovorin) by IV infusion on Days 1 and 15 of each cycle, and 5-FU at 400 mg/m2 as an IV bolus injection followed by a total of 2400 mg/m2 by CIV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump (the use of an ambulatory pump is optional). The 5-FU IV bolus (400 mg/m2) and CIV infusion (2400 mg/m2) over 46 hours is repeated on Days 15 and 16 of each cycle.

Group Type: ACTIVE_COMPARATOR

FOLFIRI

Intervention Type: DRUG

FOLFIRI will be administered as IV infusion on Days 1 and 15 of each cycle, and 5-FU at 400 mg/m\^2 as an IV bolus injection followed by a total of 2400 mg/m2 by CIV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump. The 5-FU IV bolus (400 mg/m\^2) and CIV infusion (2400 mg/m\^2) over 46 hours is repeated on Days 15 and 16 of each cycle.

E7820

E7820 is administered orally in tablet form once daily, every day of each 28-day treatment cycle. For the Phase Ib portion, the doses will be 40 mg/day, 70 mg/day, and 100 mg/day, and for the Phase II portion, the dose will be the MTD recommended Phase IB dose in combination with FOLFIRI, as determined during the Phase Ib portion of the study.

Group Type: EXPERIMENTAL

FOLFIRI

Intervention Type: DRUG

FOLFIRI will be administered as IV infusion on Days 1 and 15 of each cycle, and 5-FU at 400 mg/m\^2 as an IV bolus injection followed by a total of 2400 mg/m2 by CIV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump. The 5-FU IV bolus (400 mg/m\^2) and CIV infusion (2400 mg/m\^2) over 46 hours is repeated on Days 15 and 16 of each cycle.

E7820

Intervention Type: DRUG

E7820 will be administered orally in tablet form once daily, every day of each 28-day treatment cycle.

FOLFIRI plus Bevacizumab

Bevacizumab at 5 mg/kg (IV infusion) on Days 1 and 15 of each 28-day treatment cycle

Group Type: EXPERIMENTAL

FOLFIRI

Intervention Type: DRUG

FOLFIRI will be administered as IV infusion on Days 1 and 15 of each cycle, and 5-FU at 400 mg/m\^2 as an IV bolus injection followed by a total of 2400 mg/m2 by CIV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump. The 5-FU IV bolus (400 mg/m\^2) and CIV infusion (2400 mg/m\^2) over 46 hours is repeated on Days 15 and 16 of each cycle.

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at 5 mg/kg (IV infusion) on Days 1 and 15 of each 28-day treatment cycle.

Interventions

FOLFIRI

FOLFIRI will be administered as IV infusion on Days 1 and 15 of each cycle, and 5-FU at 400 mg/m\^2 as an IV bolus injection followed by a total of 2400 mg/m2 by CIV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump. The 5-FU IV bolus (400 mg/m\^2) and CIV infusion (2400 mg/m\^2) over 46 hours is repeated on Days 15 and 16 of each cycle.

Intervention Type: DRUG

E7820

E7820 will be administered orally in tablet form once daily, every day of each 28-day treatment cycle.

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered at 5 mg/kg (IV infusion) on Days 1 and 15 of each 28-day treatment cycle.

Intervention Type: DRUG

Other Intervention Names

leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan; Avastin

Eligibility Criteria

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 alopecia;

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harish Dave

Role: STUDY_DIRECTOR

Quintiles, Inc.

Locations

Rocky Mountain Cancer Center - Midtown

Denver, Colorado, United States

Summit Medical Group

Berkeley Heights, New Jersey, United States

Hematology Oncology Associates SJ P.A.

Mount Holly, New Jersey, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

North Coast Cancer Institute

Coffs Harbour, New South Wales, Australia

Sydney Haematology & Oncology Clinic

Hornsby, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Royal Hobart Hospital

Hobart, South Australia, Australia

Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

The Austin Hospital

Epping, Victoria, Australia

Newcastle Private Hospital

Merewether, , Australia

Jawaharlal Nehru Cancer Hospital and Research Centre

Bhopal, Madhya Pradesh, India

Searoc Cancer Hosptial

Jaipur, Rajasthan, India

Gujarat Cancer & Research Institute

Ahmedabad, , India

Kidwai Institute of Oncology

Bangalore, , India

M. S. Ramaiah Memorial Hospital

Bangalore, , India

Subodh Mitra Cancer Hospital and Research centre

Kolkata, , India

Shatabdi Hospital

Nashik, , India

Deenanath Mangeshkar Hospital and Research Center

Pune, , India

Noble Hospital

Pune, , India

Christian Medical College

Vellore, , India

CCH #2 n.a. N. A. Semashko of LLC "Russian Railways"

Moscow, , Russia

City Mariinskaya Hospital

Saint Petersburg, , Russia

Scientific Research Oncology Institute named after N.N. Petr

Saint Petersburg, , Russia

Yaroslav Regional Clinical Oncology Hospital

Yaroslav, , Russia

Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU

Dnipropetrovsk, , Ukraine

Donetsk Regional Anticancer Centre

Donetsk, , Ukraine

City Clinical Hospital #2

Kharkiv, , Ukraine

The St.Inst. "S.P.Grigoriev Med. Rad.Inst. of AMS of Ukr."

Kharkiv, , Ukraine

Uzhgorod Centr.City Cl.Hosp.,City Onc.Center, UNMU,Fac.of PG

Uzhhorod, , Ukraine

Countries

United States; Australia; India; Russia; Ukraine

Other Identifiers

2009-016015-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E7820-701

Identifier Type: -

Identifier Source: org_study_id