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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01347645




Registration number
NCT01347645
Ethics application status
Date submitted
28/04/2011
Date registered
4/05/2011
Date last updated
22/06/2023

Titles & IDs
Public title
Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer
Scientific title
An Open-Label, Multicenter, Randomized Phase Ib/II Study of Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer
Secondary ID [1] 0 0
2011-001762-18
Secondary ID [2] 0 0
E7820-702
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colon Cancer 0 0
Rectal 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

Active comparator: 1 - Experimental Irinotecan plus E7820

Active comparator: 2 - FOLFIRI alone


Treatment: Drugs: FOLFIRI
Comparator dose and mode of administration The FOLFIRI regimen consists of irinotecan at 180 mg/m2 (IV infusion) on Day 1 of each 14-day cycle, leucovorin at 200 mg/m2 (400 mg/m2 if using d,l-racemic mixture of leucovorin) by IV infusion on Day 1 of each cycle, and 5-FU at 400 mg/m2 as an IV bolus injection followed by a total of 2400 mg/m2 by continuous IV infusion over 46 hours over Days 1 and 2 via an ambulatory programmable pump (the use of an ambulatory pump is optional).

Treatment: Drugs: E7820
Test product: dose and mode of administration:

E7820 is administered orally in tablet form once daily, every day of each 14-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 Pase II portion, the dose will be the MTD in combination with Irinotecan, as determined during the Phase ib portion of the study.

The irinotecan regimen consists of an irinotecan dose of 180 mg/m2 by IV infusion once every 2 weeks (Day 1 of each 14-day cycle).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Maximum Tolerated Dose (MTD) of E7820 With Irinotecan as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
Timepoint [1] 0 0
Up to 12 cycles (each cycle length =14 days)
Primary outcome [2] 0 0
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Secondary outcome [1] 0 0
Phase 2: Progression Free Survival (PFS)
Timepoint [1] 0 0
From date of randomization up to 1 year and 2 months
Secondary outcome [2] 0 0
Phase 2: Overall Survival (OS)
Timepoint [2] 0 0
From date of randomization up to 1 year and 2 months
Secondary outcome [3] 0 0
Phase 2: Time to Progression (TTP)
Timepoint [3] 0 0
From date of randomization up to 1 year and 2 months
Secondary outcome [4] 0 0
Phase 2: Percentage of Participants With Overall Response
Timepoint [4] 0 0
From date of randomization up to 1 year and 2 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 5-FU-based therapies, including but not limited to FOLFOX, FOLFOX 4, mFOLFOX6, CapeOX, single-agent capecitabine, infusional 5-FU, or other chemotherapies. Bevacizumab, cetuximab, panitumumab, and EGFR inhibitors are allowed. Prior treatment with irinotecan or FOLFIRI is not allowed for Phase II). For Phase Ib only, up to 3 prior therapies are allowed (including non-irinotecan containing therapies and adjuvant therapy);
4. At least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) criteria;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of less than or equal to 2;
6. Patients must have adequate renal function as evidenced by serum creatinine less than 2 mg/dL and creatinine clearance greater than 50 mL/minute per the Cockcroft and Gault formula;
7. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than100 x 109/L, hemoglobin greater than or equal to 9.0 g/dL (a hemoglobin less than 9.0 g/dL at Screening is acceptable if it is corrected to greater than or equal to 9 g/dL by growth factor or transfusion prior to the first dose);
8. Patients must have adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limit of the normal range (ULN), and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (in the case of liver metastases, less than or equal to 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;
9. For patients with hypertension, it must be well controlled. If a patient presents with poorly controlled hypertension, defined as a mean systolic blood pressure greater than or equal to140 mm Hg or mean diastolic blood pressure greater than or equal to 90 mm Hg,antihypertensive medication(s) should be initiated or adjusted with a goal to control the blood pressure less than 140/90 mm Hg. Blood pressure must be reassessed on 2 occasions, consecutively, that are separated by a minimum of 24 hours;
10. 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;
11. Females of childbearing potential must have a negative serum pregnancy test at Screening;
12. Females may not be breastfeeding; Ability to understand and willingness to sign a written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 less than or equal to 1, except for peripheral neuropathy (Grade 1 and Grade 2 are permitted) and alopecia;
2. Previously received irinotecan or irinotecan derivatives in Phase II (irinotecan-containing regimens are allowed in Phase Ib);
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 in situ carcinoma of the uterine cervix; or (3) other curatively treated solid tumor with no evidence of disease for greater than or equal to 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. Serious non-healing wound, ulcer, or active bone fracture;
8. 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;
9. 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;
10. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association [NYHA] Grade greater than 2, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
11. Active hemoptysis (defined as bright red blood of 1/2 teaspoon or more) within the 30 days prior to study entry;
12. Current or recent use (within 7 days) of full-dose warfarin (except low-dose warfarin as required to maintain patency of pre-existing, permanent indwelling IV catheters). For patients receiving warfarin, International Normalization Ratio (INR) should be less than 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;
13. History of bleeding diathesis or coagulopathy;
14. Any history of cerebral vascular accident, transient ischemic attack, or Grade greater than or equal to 2 peripheral vascular disease, unless they have had no evidence of active disease for at least 6 months prior to randomization;
15. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1, unless affected area has been removed surgically;
16. Patients with organ allografts requiring immunosuppression;
17. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or active hepatitis C positive;
18. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, 5-FU, or leucovorin;
19. Hypersensitivity to sulfonamide derivatives;
20. 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
30/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/06/2015
Sample size
Target
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Coffs Harbour
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Townsville
Recruitment hospital [4] 0 0
- Elizabeth Vale
Recruitment hospital [5] 0 0
- Kurralta Park
Recruitment hospital [6] 0 0
- Woodville South
Recruitment hospital [7] 0 0
- Carlton
Recruitment hospital [8] 0 0
- Clayton
Recruitment hospital [9] 0 0
- Epping
Recruitment hospital [10] 0 0
- Frankston
Recruitment hospital [11] 0 0
- Wodonga
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
4814 - Townsville
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
5035 - Kurralta Park
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment postcode(s) [7] 0 0
3053 - Carlton
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3076 - Epping
Recruitment postcode(s) [10] 0 0
3199 - Frankston
Recruitment postcode(s) [11] 0 0
3690 - Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
North Dakota
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
LA Rioha
Country [9] 0 0
Argentina
State/province [9] 0 0
Santa FE
Country [10] 0 0
Argentina
State/province [10] 0 0
Cordoba
Country [11] 0 0
Brazil
State/province [11] 0 0
Minas Gerais
Country [12] 0 0
Brazil
State/province [12] 0 0
RIO Grande DO SUL
Country [13] 0 0
Brazil
State/province [13] 0 0
SAO Paulo
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio de Janeiro
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Arkhangelsk
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Chelyabinsk
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Sochi
Country [19] 0 0
Russian Federation
State/province [19] 0 0
St. Petersburg
Country [20] 0 0
Ukraine
State/province [20] 0 0
Dnipropetrovsk
Country [21] 0 0
Ukraine
State/province [21] 0 0
Kharkiv
Country [22] 0 0
Ukraine
State/province [22] 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
PharmaBio Development 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/NCT01347645
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/NCT01347645