Colorectal NeoplasmsPhase 2NCT00083720
Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy
A Phase 2 study testing cetuximab in people with Colorectal Neoplasms and Metastases, run by Eli Lilly and Company at 27 sites in 2 countries.
Trial summary
This is a phase II, multicenter, open-label study of cetuximab in patients with epidermal growth factor receptor (EGFR) negative, metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms, Metastases, Neoplasm
- What is being tested?
- cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 27 sitesin 2 countries
- Study dates
- Oct 2004to Apr 2008
- Phase
- Phase 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
- Provided signed written informed consent.
- Histologically- or pathologically- confirmed metastatic colorectal carcinoma;
- Documented PD after treatment with at least one standard chemotherapy regimen for metastatic colorectal carcinoma;
- The chemotherapy regimen on which the patient progressed, must have included a fluoropyrimidine;
- Bidimensionally measurable disease;
- Immunohistochemical evidence of an absence of EGFR expression, (ie, EGFR-negative). Patients who do not have tumor tissue available for EGFR testing will undergo biopsy of accessible tumor. A reference laboratory designated by ImClone will perform the EGFR assay.
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- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at study entry;
- Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 30 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or medical device, or prior radiation therapy;
- Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.
- Men and women, 18 years of age and older
Who cannot join
- Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
- Women who are pregnant or breastfeeding.
- Women with a positive pregnancy test on enrollment or prior to cetuximab administration.
- Sexually active fertile men not using effective birth control.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
- A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy;
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- A history of uncontrolled angina, arrhythmias or congestive heart failure;
- Symptomatic or uncontrolled metastases to the central nervous system. Patients receiving a glucocorticoid for central nervous system (CNS) metastases will be excluded, but those receiving anticonvulsants will be eligible.
- Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for greater than or equal to 5 years will be allowed to enter the trial;
- Inadequate hematologic function defined by an absolute neutrophil count (ANC) less than 1,500/mm3 , a platelet count less than 100,000/mm3 , or a hemoglobin level less than 9 g/dL.
- Inadequate hepatic function, defined by a total bilirubin level greater than or equal to 1.5 times the upper limit of normal (ULN) and aspartate transaminase (AST) or alanine transaminase (ALT) levels greater than or equal to 5.0 times the ULN.
- Inadequate renal function defined by a serum creatinine level greater than 1.5 times the ULN.
- Prior cetuximab or other therapy, which specifically and directly targets the EGF pathway.
- Prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy.
- Any chemotherapy not indicated in the study protocol, radiation therapy, hormonal therapy (except for physiological replacement), or any other investigational agent.
- Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- Employees of the investigator or study center with direct involvement in this study or other studies under the direction of the investigator or study center, as well as family members of the employees.
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States23 sites
ImClone Investigational Site
Ann Arbor, Michigan, 48106-0995
ImClone Investigational Site
Arlington, Texas, 76012
ImClone Investigational Site
Armonk, New York, 10504
ImClone Investigational Site
Boston, Massachusetts, 02114
ImClone Investigational Site
Bryan, Texas, 77802
ImClone Investigational Site
Campbell, California, 95008
ImClone Investigational Site
Durham, North Carolina, 27710
ImClone Investigational Site
East Setauket, New York, 11733
ImClone Investigational Site
Evansville, Indiana, 47714
ImClone Investigational Site
Gurnee, Illinois, 60031
ImClone Investigational Site
Indianapolis, Indiana, 46202
ImClone Investigational Site
Jacksonville, Florida, 32256
ImClone Investigational Site
Kalamazoo, Michigan, 49048
ImClone Investigational Site
Lexington, Kentucky, 40503
ImClone Investigational Site
Los Angeles, California, 90033
ImClone Investigational Site
Louisville, Kentucky, 40202
ImClone Investigational Site
Metairie, Louisiana, 70006
ImClone Investigational Site
Orlando, Florida, 32804
ImClone Investigational Site
Ormond Beach, Florida, 32174
ImClone Investigational Site
Sellingsgrove, Pennsylvania, 17870
ImClone Investigational Site
Soquel, California, 95073
ImClone Investigational Site
St Louis, Missouri, 63110
ImClone Investigational Site
Temple, Texas, 76508
Canada4 sites
ImClone Investigational Site
Oshawa, Ontario, L1G 2B9
ImClone Investigational Site
Ottawa, Ontario, K1H 1C4
ImClone Investigational Site
Toronto, Ontario, M4N 3M5
ImClone Investigational Site
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase II Multicenter Study of Erbitux (Cetuximab) in Patients With Refractory, EGFR-Negative Metastatic Colorectal Carcinoma
This is a phase II, multicenter, open-label study of cetuximab in patients with epidermal growth factor receptor (EGFR) negative, metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine. Target enrollment is 80 evaluable patients.
Patients with EGFR-negative metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine, will receive an initial dose of cetuximab, 400 mg/m2 , intravenously (i.v.) over 120 minutes, followed by weekly treatment with cetuximab, 250 mg/m2 i.v. over 60 minutes. Patients who experience unacceptable toxicity or who have progressive disease (PD) will not receive further cetuximab therapy.
Patients will be evaluated for a tumor response at a minimum of every 6 weeks while on cetuximab therapy. Patients with stable disease (SD), partial response (PR), or a complete response (CR) may continue to receive weekly cetuximab therapy, unless they are dose-delayed or discontinued because of toxicity. Patients who have a PR or CR must have a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response. To evaluate the objective response rate, a single-stage design will be used in this study.
- Conditions
- Colorectal Neoplasms, Metastases, Neoplasm
- Being tested
- cetuximab
- Keywords
- EGFR-undetectable, Metastatic Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Also called Erbitux™
Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| cetuximab | Experimental | Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes Receives: Biological: cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an Overall Resonse
Determine the response rate (complete response [CR] and partial response [PR]) in patients with epidermal growth factor receptor (EGFR)-negative metastatic colorectal carcinoma treated with cetuximab, as classified by the investigator according to the World Health Organization (WHO) criteria. The calculation was the total number of patients with CR or PR divided by the total number of patients treated.
Measured: Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.
Number of Participants With Adverse Events
Reported adverse events (AEs) per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities dictionary. The National Cancer Insititute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).
Measured: An adverse event (AE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Number of Participants With Serious Adverse Events
Reported SAEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities. The NCI-CTCAE Version 3.0 was used to grade all SAEs. An SAE was any untoward medical occurrence that resulted in death, persistent/significant disability/incapacity, was life threatening, required inpatient hospitalization or caused prolongation of existing hospitalization,congenital anomaly/birth defect, or any important medical event.
Measured: A serious adverse event (SAE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Secondary outcomes (4)
Percentage of Participants With Disease Control (CR, PR, or SD)
This is the total number of patients with a best overall response of CR, PR, and stable disease (SD) divided by the total number of patients treated.
Measured: Tumor evaluations were performed at a minimum of every 6 weeks while on cetuximab therapy. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response.
Duration of Response
In patients with a best overall response of CR or PR, the duration of response is measured from the date criteria are first met for CR or PR, until the first date that Progressive Disease (PD) is objectively documented or death occurs. Duration of response of living patients with no evidence of PD was censored on the date of their last tumor assessment.
Measured: The duration of response was measured from the date of response to the first date of PD (range 2 to 7 months).
Time to Progression
This measure was defined as the time from the first day of treatment until the date of PD. Deaths without objective progression were censored. Patients who did not progress were censored at their last day of tumor assessment.
Measured: Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months).
Overall Survival
This measure is defined as the time from the first day of therapy to the date of death. Survival of living patients or those lost to follow-up were censored on the last date the patients were known to be alive.
Measured: Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2004 (estimated)
- Study startOct 2004
- Primary completionApr 2008
- Study completionApr 2008
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 NeoplasmsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Investigators
- E-mail: ClinicalTrials@ ImClone.com, Study chair, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083720
- Sponsor's protocol ID
- CP02-0451
- Status last verified
- May 2011
- First submitted
- 28 May 2004
- Last updated
- 25 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multicenter Study of Erbitux (Cetuximab) in Patients With Refractory, EGFR-Negative Metastatic Colorectal Carcinoma
- ClinicalTrials.gov ID
- NCT00083720
- Acronym / sponsor ID
- CP02-0451
- Conditions
- Colorectal Neoplasms, Metastases, Neoplasm
- Keywords
- EGFR-undetectable, Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- Oct 2004
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 2 Jun 2004 (estimated)
- Results
- Posted 23 Oct 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II, multicenter, open-label study of cetuximab in patients with epidermal growth factor receptor (EGFR) negative, metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine. Target enrollment is 80 evaluable patients.
Patients with EGFR-negative metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine, will receive an initial dose of cetuximab, 400 mg/m2 , intravenously (i.v.) over 120 minutes, followed by weekly treatment with cetuximab, 250 mg/m2 i.v. over 60 minutes. Patients who experience unacceptable toxicity or who have progressive disease (PD) will not receive further cetuximab therapy.
Patients will be evaluated for a tumor response at a minimum of every 6 weeks while on cetuximab therapy. Patients with stable disease (SD), partial response (PR), or a complete response (CR) may continue to receive weekly cetuximab therapy, unless they are dose-delayed or discontinued because of toxicity. Patients who have a PR or CR must have a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response. To evaluate the objective response rate, a single-stage design will be used in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cetuximab | Experimental | Biological: cetuximabInitial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provided signed written informed consent.
- Histologically- or pathologically- confirmed metastatic colorectal carcinoma;
- Documented PD after treatment with at least one standard chemotherapy regimen for metastatic colorectal carcinoma;
- The chemotherapy regimen on which the patient progressed, must have included a fluoropyrimidine;
- Bidimensionally measurable disease;
Key exclusion criteria (17 listed)
- Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
- Women who are pregnant or breastfeeding.
- Women with a positive pregnancy test on enrollment or prior to cetuximab administration.
- Sexually active fertile men not using effective birth control.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
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 |
|---|---|---|
| cetuximabAlso: Erbitux™Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes | Biological | cetuximab |
Primary outcome
Percentage of Participants With an Overall Resonse
Time frame: Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.
Determine the response rate (complete response [CR] and partial response [PR]) in patients with epidermal growth factor receptor (EGFR)-negative metastatic colorectal carcinoma treated with cetuximab, as classified by the investigator according to the World Health Organization (WHO) criteria. The calculation was the total number of patients with CR or PR divided by the total number of patients treated.
Number of Participants With Adverse Events
Time frame: An adverse event (AE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Reported adverse events (AEs) per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities dictionary. The National Cancer Insititute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).
Number of Participants With Serious Adverse Events
Time frame: A serious adverse event (SAE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Reported SAEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities. The NCI-CTCAE Version 3.0 was used to grade all SAEs. An SAE was any untoward medical occurrence that resulted in death, persistent/significant disability/incapacity, was life threatening, required inpatient hospitalization or caused prolongation of existing hospitalization,congenital anomaly/birth defect, or any important medical event.
4 secondary outcomes
Percentage of Participants With Disease Control (CR, PR, or SD)
Time frame: Tumor evaluations were performed at a minimum of every 6 weeks while on cetuximab therapy. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response.
Duration of Response
Time frame: The duration of response was measured from the date of response to the first date of PD (range 2 to 7 months).
Time to Progression
Time frame: Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months).
Overall Survival
Time frame: Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2011.
- 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.
E-mail: ClinicalTrials@ ImClone.com study chair
Eli Lilly and Company
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab in people with Colorectal Neoplasms and Metastases, run by Eli Lilly and Company at 27 sites in 2 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 10 inclusion and 17 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 25 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada. 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 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 23 Oct 2009). 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?
Percentage of Participants With an Overall Resonse (time frame: Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.). The study lists 3 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 25 May 2011.