Colorectal CarcinomaPhase 1NCT01286818
A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)
A Phase 1 study testing Ramucirumab (IMC-1121B), Irinotecan and levofolinate in people with Colorectal Carcinoma, run by Eli Lilly and Company at 3 sites in Japan.
Trial summary
The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Colorectal Carcinoma
- What is being tested?
- Ramucirumab (IMC-1121B), Irinotecan and levofolinate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesJapan
- Study dates
- Feb 2011to Mar 2012
- Phase
- Phase 1
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is Japanese
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Has histologically or cytologically confirmed CRC
- Has metastatic disease that is not amenable to potentially curative resection
- Has received no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)
- Has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and has experienced disease progression during first-line therapy, or disease progression within 6 months after the last dose of first-line therapy, or discontinued part or all of first-line therapy due to toxicity and experienced disease progression within 6 months after the last dose of first-line therapy. Participants must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy in order to enroll.
- Has adequate hepatic, renal, hematologic, and coagulation function
- The participant's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate <1000 milligrams (mg) of protein in 24 hours to allow participation in the study
Who cannot join
- Has received bevacizumab within 28 days prior to study registration
- Has received chemotherapy within 21 days prior to study registration
- Has received any previous systemic therapy (other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine) for first-line treatment of metastatic CRC
- The participant experienced any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event; Grade 4 hypertension; Grade 4 proteinuria; a Grade 3-4 bleeding event; or bowel perforation
- Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration
- Has undergone major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to study registration
Show all 24Show fewer
- Has elective or planned surgery to be conducted during the trial
- Has a history of deep vein thrombosis or pulmonary embolism within the past 12 months
- Has experienced any arterial thrombotic event within the past 12 months
- Participant is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents
- Participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents [Aspirin up to 325 milligrams per day (mg/day) permitted]
- Has a significant bleeding disorder or has had a significant (Grade 3 or higher) bleeding event within 3 months prior to registration date
- Has a history of gastrointestinal perforation and/or fistulae within 6 months prior to registration date
- Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
- Has uncontrolled arterial hypertension despite standard medical management
- Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to study registration
- Has an acute/subacute bowel obstruction or history of clinically significant chronic diarrhea
- Has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to registration date
- The participant has either peptic ulcer disease associated with a bleeding event or known active diverticulitis
- Has an active infection requiring antibiotic, antifungal, or antiviral therapy
- Has known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
- Has known leptomeningeal or brain metastases or uncontrolled spinal cord compression
- Has a known history of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*6/*6; UGT1A1*28/*28 or UGT1A1*6/*28
- Has previous or concurrent malignancy, except for basal or squamous cell skin cancer and/or in situ carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years
Trial locations and contacts
3 sites in 1 country.
Japan3 sites
ImClone Investigational Site
Chiba, 277-8577
ImClone Investigational Site
Osaka, 569-8686
ImClone Investigational Site
Shizuoka, 411-8777
About this study
Official title: A Phase 1b Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) Drug Product in Japanese Subjects With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced colorectal carcinoma (CRC).
- Conditions
- Colorectal Carcinoma
- Being tested
- Ramucirumab (IMC-1121B), Irinotecan, levofolinate, 5-Fluorouracil (5-FU)
- Keywords
- Colon Cancer, Rectal Cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ramucirumab (IMC-1121B)Biological
Also called IMC-1121B, Ramucirumab, LY3009806
Ramucirumab (IMC-1121B): Intravenous (IV) infusions, 8 milligrams per kilogram (mg/kg) every 2 weeks
IrinotecanDrug
IV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeks
levofolinateDrug
IV infusion, 200 mg/m² every 2 weeks
5-Fluorouracil (5-FU)Drug
400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRI plus Ramucirumab (IMC-1121B) | Experimental | Not described Receives: Biological: Ramucirumab (IMC-1121B); Drug: Irinotecan; Drug: levofolinate; Drug: 5-Fluorouracil (5-FU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count <1.0x10^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein >3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
Measured: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. Events related to Irinotecan, Levofolinate, and 5-fluorouracil (5-FU) were reported separately. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Measured: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up
Secondary outcomes (7)
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Measured: Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]
Maximum Concentration (Cmax) of Ramucirumab
The Cmax of ramucirumab in serum on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered Cmax at steady state (Cmax,ss), is reported.
Measured: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Area Under the Curve (AUC) of Ramucirumab
Reported for Day 1, Cycle 1 is AUC from time 0 extrapolated to infinity [AUC(0-inf)] and for Day 1, Cycle 5 is AUC over the dosing interval at steady state AUC(tau,ss).
Measured: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Half Life (t1/2) of Ramucirumab
t1/2 is the time required for the plasma/serum concentration to decrease 50%.
Measured: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Clearance (CL) of Ramucirumab
The total body CL of ramucirumab on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered CL at steady state (CLss), is reported.
Measured: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Steady State Volume of Distribution (Vss) of Ramucirumab
Vss is the theoretical volume in which the total amount of study drug would need to be uniformly distributed during steady state to produce the same concentration as it is in plasma/serum.
Measured: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Best overall response evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression). Stable Disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.
Measured: Every 8 weeks until PD (up to 49 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2011 (estimated)
- Study startFeb 2011
- Primary completionFeb 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01286818
- Sponsor's protocol ID
- 14223
- Other IDs
- CP12-1029, 14T-IE-JVBY
- Status last verified
- Oct 2014
- First submitted
- 25 Jan 2011
- Last updated
- 6 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) Drug Product in Japanese Subjects With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
- ClinicalTrials.gov ID
- NCT01286818
- Acronym / sponsor ID
- 14223
- Conditions
- Colorectal Carcinoma
- Keywords
- Colon Cancer, Rectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Feb 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 31 Jan 2011 (estimated)
- Results
- Posted 6 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced colorectal carcinoma (CRC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFIRI plus Ramucirumab (IMC-1121B) | Experimental | Biological: Ramucirumab (IMC-1121B), Drug: Irinotecan, Drug: levofolinate, Drug: 5-Fluorouracil (5-FU) |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participant is Japanese
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Has histologically or cytologically confirmed CRC
- Has metastatic disease that is not amenable to potentially curative resection
- Has received no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)
Key exclusion criteria (24 listed)
- Has received bevacizumab within 28 days prior to study registration
- Has received chemotherapy within 21 days prior to study registration
- Has received any previous systemic therapy (other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine) for first-line treatment of metastatic CRC
- The participant experienced any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event; Grade 4 hypertension; Grade 4 proteinuria; a Grade 3-4 bleeding event; or bowel perforation
- Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ramucirumab (IMC-1121B)Also: IMC-1121B, Ramucirumab, LY3009806Ramucirumab (IMC-1121B): Intravenous (IV) infusions, 8 milligrams per kilogram (mg/kg) every 2 weeks | Biological | FOLFIRI plus Ramucirumab (IMC-1121B) |
| IrinotecanIV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeks | Drug | FOLFIRI plus Ramucirumab (IMC-1121B) |
| levofolinateIV infusion, 200 mg/m² every 2 weeks | Drug | FOLFIRI plus Ramucirumab (IMC-1121B) |
| 5-Fluorouracil (5-FU)400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks | Drug | FOLFIRI plus Ramucirumab (IMC-1121B) |
Primary outcome
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
Time frame: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count <1.0x10^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein >3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Time frame: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up
Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. Events related to Irinotecan, Levofolinate, and 5-fluorouracil (5-FU) were reported separately. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
7 secondary outcomes
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Time frame: Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]
Maximum Concentration (Cmax) of Ramucirumab
Time frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Area Under the Curve (AUC) of Ramucirumab
Time frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Half Life (t1/2) of Ramucirumab
Time frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Clearance (CL) of Ramucirumab
Time frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Steady State Volume of Distribution (Vss) of Ramucirumab
Time frame: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Time frame: Every 8 weeks until PD (up to 49 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ramucirumab (IMC-1121B), Irinotecan and levofolinate in people with Colorectal Carcinoma, run by Eli Lilly and Company at 3 sites in Japan.
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 8 inclusion and 24 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: finished, as of the sponsor's last update on 6 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Japan. 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 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.
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 6 Oct 2014). 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?
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period (time frame: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=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?
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 6 Oct 2014.