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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01133990




Registration number
NCT01133990
Ethics application status
Date submitted
21/05/2010
Date registered
31/05/2010
Date last updated
7/11/2023

Titles & IDs
Public title
FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer
Scientific title
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
Secondary ID [1] 0 0
2009-016015-37
Secondary ID [2] 0 0
E7820-701
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FOLFIRI
Treatment: Drugs - E7820
Treatment: Drugs - Bevacizumab

Active comparator: 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.

Experimental: 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.

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


Treatment: Drugs: 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.

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

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered at 5 mg/kg (IV infusion) on Days 1 and 15 of each 28-day treatment cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (each cycle length=28 days)
Primary outcome [2] 0 0
Phase 1b: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
Primary outcome [3] 0 0
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Timepoint [3] 0 0
From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
Primary outcome [4] 0 0
Phase 1b: Number of Participants With Clinically Significant Changes in Physical Examinations
Timepoint [4] 0 0
From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
Primary outcome [5] 0 0
Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Parameter
Timepoint [5] 0 0
From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
Secondary outcome [1] 0 0
Phase 2: Progression-Free Survival (PFS)
Timepoint [1] 0 0
From the date of randomization to date of PD or death (whichever occurred first), up to 11 months
Secondary outcome [2] 0 0
Phase 2: Time to Progression (TTP)
Timepoint [2] 0 0
From date randomization to date of PD or death, up to 11 months
Secondary outcome [3] 0 0
Phase 2: Objective Response Rate (ORR)
Timepoint [3] 0 0
From date of treatment start to until date of first PD or death (whichever occurred first), up to 11 months
Secondary outcome [4] 0 0
Phase 2: Overall Survival (OS)
Timepoint [4] 0 0
From date of randomization to date of PD or death, up to 11 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/03/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/02/2011
Sample size
Target
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
North Coast Cancer Institute - Coffs Harbour
Recruitment hospital [2] 0 0
Sydney Haematology & Oncology Clinic - Hornsby
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Queen Elizabeth Hospital - Woodville South
Recruitment hospital [7] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
The Austin Hospital - Epping
Recruitment hospital [9] 0 0
Newcastle Private Hospital - Merewether
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2077 - Hornsby
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3076 - Epping
Recruitment postcode(s) [9] 0 0
2305 - Merewether
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
India
State/province [6] 0 0
Madhya Pradesh
Country [7] 0 0
India
State/province [7] 0 0
Rajasthan
Country [8] 0 0
India
State/province [8] 0 0
Ahmedabad
Country [9] 0 0
India
State/province [9] 0 0
Bangalore
Country [10] 0 0
India
State/province [10] 0 0
Kolkata
Country [11] 0 0
India
State/province [11] 0 0
Nashik
Country [12] 0 0
India
State/province [12] 0 0
Pune
Country [13] 0 0
India
State/province [13] 0 0
Vellore
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Moscow
Country [15] 0 0
Russian Federation
State/province [15] 0 0
St Petersburg
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Yaroslav
Country [17] 0 0
Ukraine
State/province [17] 0 0
Dnipropetrovsk
Country [18] 0 0
Ukraine
State/province [18] 0 0
Donetsk
Country [19] 0 0
Ukraine
State/province [19] 0 0
Kharkiv
Country [20] 0 0
Ukraine
State/province [20] 0 0
Uzhgorod

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Quintiles, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01133990
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Harish Dave
Address 0 0
Quintiles, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01133990