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Colon CancerPhase 1/2NCT01347645

Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer

A Phase 1/2 study testing FOLFIRI and E7820 in people with Colon Cancer and Rectal Cancer, run by Eisai Inc. at 38 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer, Rectal Cancer
What is being tested?
FOLFIRI and E7820
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
38 sitesin 6 countries
Study dates
30 Sep 2011to 22 Jun 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients may be entered in the study only if they meet all of the following criteria:
  • Male or female patient greater than or equal to 18 years of age;
  • Histologically or cytologically confirmed nonresectable locally advanced or metastatic colorectal adenocarcinoma;
  • 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);
  • At least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) criteria;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of less than or equal to 2;
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  • 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;
  • 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);
  • 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;
  • 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;
  • 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;
  • Females of childbearing potential must have a negative serum pregnancy test at Screening;
  • Females may not be breastfeeding; Ability to understand and willingness to sign a written informed consent.

Who cannot join

  • 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;
  • Previously received irinotecan or irinotecan derivatives in Phase II (irinotecan-containing regimens are allowed in Phase Ib);
  • Previously received anti-alpha 2 integrin therapy;
  • 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;
  • 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;
  • Are currently receiving any other anticancer treatment;
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  • Serious non-healing wound, ulcer, or active bone fracture;
  • 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;
  • 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;
  • 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);
  • Active hemoptysis (defined as bright red blood of 1/2 teaspoon or more) within the 30 days prior to study entry;
  • 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;
  • History of bleeding diathesis or coagulopathy;
  • 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;
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1, unless affected area has been removed surgically;
  • Patients with organ allografts requiring immunosuppression;
  • Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or active hepatitis C positive;
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, 5-FU, or leucovorin;
  • Hypersensitivity to sulfonamide derivatives;
  • Have any medical condition that would interfere with the conduct of the study.

Trial locations and contacts

38 sites in 6 countries.

38 sites in 6 countries

Australia11 sites

  • Study site

    Carlton, Victoria, 3053

  • Study site

    Clayton, Victoria, 3168

  • Study site

    Coffs Harbour, New South Wales, 2450

  • Study site

    Concord, New South Wales, 2139

  • Study site

    Elizabeth Vale, South Australia, 5112

  • Study site

    Epping, Victoria, 3076

  • Study site

    Frankston, Victoria, 3199

  • Study site

    Kurralta Park, South Australia, 5035

  • Study site

    Townsville, Queensland, 4814

  • Study site

    Wodonga, Victoria, 3690

  • Study site

    Woodville South, South Australia, 5011

Other trials in Australia

Brazil7 sites

  • Study site

    Belo Horizonte, Minas Gerais

  • Study site

    Jaú, São Paulo

  • Study site

    Novo Hamburgo, Rio Grande do Sul

  • Study site

    Passo Fundo, Rio Grande do Sul

  • Study site

    Port Alegre, Rio Grande do Sul

  • Study site

    Porto Alegre, Rio Grande do Sul

  • Study site

    Rio de Janeiro

Other trials in Brazil

United States6 sites

  • Study site

    Ann Arbor, Michigan, 48109

  • Study site

    Atlanta, Georgia, 30341

  • Study site

    Berkeley Heights, New Jersey, 7922

  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Bismarck, North Dakota, 58501

  • Study site

    West Palm Beach, Florida, 33401

Other trials in United States

Russia6 sites

  • Study site

    Arkhangelsk, 163045

  • Study site

    Chelyabinsk, 454087

  • Study site

    Moscow, 115478

  • Study site

    Saint Petersburg, 195067

  • Study site

    Saint Petersburg, 197758

  • Study site

    Sochi, 354057

Other trials in Russia

Argentina4 sites

  • Study site

    Ciudad Autonoma de Buenos Aires, Buenos Aires

  • Study site

    Córdoba

  • Study site

    La Rioja, LA Rioha

  • Study site

    Rosario, Santa Fe Province

Other trials in Argentina

Ukraine4 sites

  • Study site

    Dnipropetrovsk, 49102

  • Study site

    Kharkiv, 61024

  • Study site

    Kharkiv, 61037

  • Study site

    Uzhhorod, 88000

Other trials in Ukraine

About this study

Official 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

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.

Read the detailed description

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 2-arm design. Approximately 95 patients with measurable, nonresectable locally advanced or metastatic colorectal adenocarcinoma, who have failed first-line chemotherapy, will be enrolled in the study (approximately 12 to 15 patients in the Phase Ib portion and 80 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 12 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 12 cycles, patients 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 12 cycles, further chemotherapy may be considered following discussion with the medical monitor and sponsor.

Being tested
FOLFIRI, E7820
Keywords
locally advanced, metastatic colon, rectal cancer
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFIRIDrug

    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).

  • E7820Drug

    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).

Study groups in NCT01347645
Study groupRoleWhat they receive
1Active comparatorExperimental Irinotecan plus E7820
Receives: Drug: E7820
2Active comparatorFOLFIRI alone
Receives: Drug: FOLFIRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    MTD: maximum dose that was determined to be safe and tolerable for Phase 2.If two dose limiting toxicities (DLTs) occurred at any dose level,MTD: preceding dose/intermediate dose.DLT was graded according to CTCAE v4.0. Includes >= Grade 3(G3) peripheral neuropathy,>=G3 nausea/vomiting despite optimal anti-emetic treatment, any other non-hematologic toxicity of >=G3(except alopecia, single abnormal laboratory values Investigator judged unlikely related to study therapy, had no clinical correlate, resolved in 7 days, hypersensitivity reaction to any of compounds),Grade 4 neutropenia lasting over 7 days,febrile neutropenia(defined as fever >=38.5 degrees Celsius with absolute neutrophil count below 1.0*10^9 per liter, G3 thrombocytopenia with nontraumatic bleeding(without therapeutic systemic anticoagulation)requiring platelet transfusion,Grade 4 thrombocytopenia (with/without nontraumatic bleeding),any study drug-related death,other toxicity dose escalation committee believed to be DLT.

    Measured: Up to 12 cycles (each cycle length =14 days)

  2. Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    TEAE is defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. Number of participants with TEAEs are reported based on safety assessments of laboratory tests, physical examination, examining bowel movements, regular measurement of vital signs, eastern cooperative oncology group-performance status and electrocardiogram parameter values. SAE is any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; is congenital anomaly/birth defect or medically important due to other reasons than above mentioned criteria. Number of participants with TEAEs and SAEs were reported.

    Measured: From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)

Secondary outcomes (4)

  1. Phase 2: Progression Free Survival (PFS)

    PFS is defined as the time from the date of randomization of a participant until the sooner of (1) the date of first documented progression of such participant's disease (PD) based on Investigator assessments according to response evaluation criteria in solid tumor (RECIST) version (v) 1.1. or; (2) the date of such participant's death due to any cause. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

    Measured: From date of randomization up to 1 year and 2 months

  2. Phase 2: Overall Survival (OS)

    OS is defined as time from the date of randomization of a participant until the date of death of such participant, regardless of the actual cause of the participant's death.

    Measured: From date of randomization up to 1 year and 2 months

  3. Phase 2: Time to Progression (TTP)

    TTP is defined as time from the date of randomization of a participant until the date of first documented progression of such participant's disease. PD is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking in reference the smallest summed longest diameters on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.

    Measured: From date of randomization up to 1 year and 2 months

  4. Phase 2: Percentage of Participants With Overall Response

    ORR is defined as percentage of participants in the study whose best overall response is either complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as complete disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to less than 10 mm. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline summed longest diameters.

    Measured: From date of randomization up to 1 year and 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2011 (estimated)
  2. Study start30 Sep 2011
  3. Primary completion22 Jun 2015
  4. Study completion22 Jun 2015

Why it stopped: The study was terminated by the Sponsor due to E7820 plus irinotecan being potentially inferior to FOLFIRI

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01347645
Sponsor's protocol ID
E7820-702
Other IDs
2011-001762-18
Status last verified
Jun 2023
First submitted
28 Apr 2011
Last updated
22 Jun 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing FOLFIRI and E7820 in people with Colon Cancer and Rectal Cancer, run by Eisai Inc. at 38 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Australia, Brazil, United States, Russia, Argentina and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 12 cycles (each cycle length =14 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01347645.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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