Clinical trial NCT01133990: FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2010-05-31
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 (each cycle length=28 days)
measure: Phase 1b: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
timeFrame: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
measure: Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
timeFrame: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
measure: Phase 1b: Number of Participants With Clinically Significant Changes in Physical Examinations
timeFrame: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
measure: Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Parameter
timeFrame: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
Secondary outcomes:
measure: Phase 2: Progression-Free Survival (PFS)
timeFrame: From the date of randomization to date of PD or death (whichever occurred first), up to 11 months
measure: Phase 2: Time to Progression (TTP)
timeFrame: From date randomization to date of PD or death, up to 11 months
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: From date of treatment start to until date of first PD or death (whichever occurred first), up to 11 months
measure: Phase 2: Overall Survival (OS)
timeFrame: From date of randomization to date of PD or death, up to 11 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center - Midtown
state: Colorado
city: Berkeley Heights
country: United States
facility: Summit Medical Group
state: New Jersey
city: Mount Holly
country: United States
facility: Hematology Oncology Associates SJ P.A.
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Coffs Harbour
country: Australia
facility: North Coast Cancer Institute
state: New South Wales
city: Hornsby
country: Australia
facility: Sydney Haematology & Oncology Clinic
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: South Australia
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Epping
country: Australia
facility: The Austin Hospital
state: Victoria
city: Merewether
country: Australia
facility: Newcastle Private Hospital
city: Bhopal
country: India
facility: Jawaharlal Nehru Cancer Hospital and Research Centre
state: Madhya Pradesh
city: Jaipur
country: India
facility: Searoc Cancer Hosptial
state: Rajasthan
city: Ahmedabad
country: India
facility: Gujarat Cancer & Research Institute
city: Bangalore
country: India
facility: Kidwai Institute of Oncology
city: Bangalore
country: India
facility: M. S. Ramaiah Memorial Hospital
city: Kolkata
country: India
facility: Subodh Mitra Cancer Hospital and Research centre
city: Nashik
country: India
facility: Shatabdi Hospital
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Center
city: Pune
country: India
facility: Noble Hospital
city: Vellore
country: India
facility: Christian Medical College
city: Moscow
country: Russian Federation
facility: CCH #2 n.a. N. A. Semashko of LLC "Russian Railways"
city: St Petersburg
country: Russian Federation
facility: City Mariinskaya Hospital
city: St Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute named after N.N. Petr
city: Yaroslav
country: Russian Federation
facility: Yaroslav Regional Clinical Oncology Hospital
city: Dnipropetrovsk
country: Ukraine
facility: Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU
city: Donetsk
country: Ukraine
facility: Donetsk Regional Anticancer Centre
city: Kharkiv
country: Ukraine
facility: City Clinical Hospital #2
city: Kharkiv
country: Ukraine
facility: The St.Inst. "S.P.Grigoriev Med. Rad.Inst. of AMS of Ukr."
city: Uzhgorod
country: Ukraine
facility: Uzhgorod Centr.City Cl.Hosp.,City Onc.Center, UNMU,Fac.of PG
Study officials:
affiliation: Quintiles, Inc.
name: Harish Dave
role: STUDY_DIRECTOR
References: