CancerPhase 1NCT00110357
Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
A Phase 1 study testing Cetuximab + Irinotecan in people with Cancer and Refractory Solid Tumor, run by Eli Lilly and Company at 9 sites in United States.
Trial summary
The purpose of this clinical research study is to establish the maximum tolerated dose and recommended Phase II dose of Erbitux™ in combination with Irinotecan in pediatric and adolescent patients with refractory solid tumors. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Cancer, Refractory Solid Tumor
- What is being tested?
- Cetuximab + Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 9 sitesUnited States
- Study dates
- Aug 2005to Mar 2008
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically or cytologically confirmed diagnosis of a solid tumor which has progressed on, or following standard therapy, or for which no standard effective therapy is known.
- Children age 1-18 years.
Who cannot join
- Presence of active infection.
- Requirement to receive concurrent chemotherapy immunotherapy, radiotherapy, or any other investigational drug while on study.
- Inadequate bone marrow, hepatic, or renal function.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Children'S Healthcare Of Atlanta
Atlanta, Georgia, 30322
Sidney Kimmel Cancer Center At Johns Hopkins
Baltimore, Maryland, 21231
The Children'S Hospital
Denver, Colorado, 80218
University Of Florida
Gainesville, Florida, 32610
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, 77030
Vanderbilt University Medical Center Infectious Diseases
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Phoenix Children'S Hospital
Phoenix, Arizona, 85016
University Of Arizona Health Sciences Center
Tucson, Arizona, 85724
About this study
Official title: Phase I Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
The purpose of this clinical research study is to establish the maximum tolerated dose and recommended Phase II dose of Erbitux™ in combination with Irinotecan in pediatric and adolescent patients with refractory solid tumors.
- Conditions
- Cancer, Refractory Solid Tumor
- Being tested
- Cetuximab + Irinotecan
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cetuximab + IrinotecanDrug
Intravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 16 or 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days.
Cetuximab + IrinotecanDrug
Intravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | 1-12 years old Receives: Drug: Cetuximab + Irinotecan |
| Group B | Active comparator | 13-18 years old Receives: Drug: Cetuximab + Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
MTD of cetuximab intravenous (IV) weekly + irinotecan IV x5 days x2 weeks (in a 3-week cycle) and RPIID of cetuximab IV weekly, as measured by dose-limiting toxicities (see outcome measure 2)
Measured: Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.
Secondary outcomes (13)
Number of Participants With a Dose-Limiting Toxicity
Dose-limiting toxicities (DLTs)=serious drug side effects preventing further dose escalation. If 1 of the first 3 subjects developed a DLT during cycle 1 up to 3 additional subjects were enrolled at that dose level. The maximum dose level at which DLTs occurred in fewer than 2 out of 3 to 6 subjects was defined as the Maximum Tolerated Dose (MTD).
Measured: Prior to each 21-day cycle until dose-limiting toxicities
Maximum Plasma Concentration (Cmax)
The single dose pharmacokinetics (PK) of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; Cmax was evaluated based on concentration-time profile.
Measured: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Area Under the Curve, Extrapolated to Infinity (AUC[INF])
The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; AUC(INF) was evaluated based on concentration-time profile.
Measured: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Terminal Half-Life (T-Half)
The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; T-half was evaluated based on concentration-time profile.
Measured: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Clearance Corrected for Body Surface Area (CL/BSA)
The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; CL/BSA was evaluated based on concentration-time profile.
Measured: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)
The single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; VSS/BSA was evaluated based on concentration-time profile.
Measured: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Tumor Response
Non-central nervous system (CNS) tumors evaluated using Response Evaluation Criteria In Solid Tumors (RECIST), criteria to define when cancer patients improve ("respond"), stay the same ("stable"), or worsen ("progression"). CNS tumors evaluated based on measurements by investigator, dependence on corticosteroids, and neurologic exam.
Measured: Every other 21-day cycle
Human Anti-cetuximab Antibody (HACA) Response
In order to be considered positive for anti-cetuximab a sample had to: 1) be evaluable (i.e., have a pre and at least one post-treatment timepoint), 2) have an anti-cetuximab value > 7 ng/mL and 3) have a post-treatment sample at least twice the pre-treatment level.
Measured: Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Toxicity assessments performed at least weekly from the 1st dose of study drug until at least 30 days after the final dose of study drug and thereafter every 4 weeks until all study-related toxicities resolved, returned to baseline, or were deemed irreversible, whichever was longer. Grade 3=severe AE; grade 4=disabling or life threatening.
Measured: Weekly throughout the study and every 4 weeks thereafter
Grade 3-4 Laboratory Abnormalities - Leukopenia
Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Measured: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3-4 Laboratory Abnormalities - Neutropenia
Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe and undesirable AE; Grade 4=Life-threatening or disabling AE
Measured: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3-4 Laboratory Abnormalities - Thrombocytopenia
Blood samples collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Measured: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3/4 Laboratory Abnormalities - Hypomagnesemia
Blood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Measured: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2005 (estimated)
- Study startAug 2005
- Primary completionMar 2008
- Study completionMar 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 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
- NCT00110357
- Sponsor's protocol ID
- CA225-085
- Status last verified
- Nov 2015
- First submitted
- 6 May 2005
- Last updated
- 24 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Trippett TM, Herzog C, Whitlock JA, Wolff J, Kuttesch J, Bagatell R, Hunger SP, Boklan J, Smith AA, Arceci RJ, Katzenstein HM, Harbison C, Zhou X, Lu H, Langer C, Weber M, Gore L. Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: a study of the pediatric oncology experimental therapeutic investigators' consortium. J Clin Oncol. 2009 Oct 20;27(30):5102-8. doi: 10.1200/JCO.2008.20.8975. Epub 2009 Sep 21.
PubMed 19770383
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00110357
- Acronym / sponsor ID
- CA225-085
- Conditions
- Cancer, Refractory Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 9 May 2005 (estimated)
- Results
- Posted 11 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical research study is to establish the maximum tolerated dose and recommended Phase II dose of Erbitux™ in combination with Irinotecan in pediatric and adolescent patients with refractory solid tumors.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: Cetuximab + Irinotecan1-12 years old |
| Group B | Active comparator | Drug: Cetuximab + Irinotecan13-18 years old |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Histologically or cytologically confirmed diagnosis of a solid tumor which has progressed on, or following standard therapy, or for which no standard effective therapy is known.
- Children age 1-18 years.
Key exclusion criteria (3 listed)
- Presence of active infection.
- Requirement to receive concurrent chemotherapy immunotherapy, radiotherapy, or any other investigational drug while on study.
- Inadequate bone marrow, hepatic, or renal function.
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 |
|---|---|---|
| Cetuximab + IrinotecanIntravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 16 or 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days. | Drug | Group A |
| Cetuximab + IrinotecanIntravenous (IV) cetuximab 75 - 250 mg/m2 depending on dose escalation for MTD, weekly; irinotecan was administered at a dose of 20 mg/m2 or per dose escalation, administered x5 days x2 weeks, separated by 2 days off, every 21 days. | Drug | Group B |
Primary outcome
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
Time frame: Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.
MTD of cetuximab intravenous (IV) weekly + irinotecan IV x5 days x2 weeks (in a 3-week cycle) and RPIID of cetuximab IV weekly, as measured by dose-limiting toxicities (see outcome measure 2)
13 secondary outcomes
Number of Participants With a Dose-Limiting Toxicity
Time frame: Prior to each 21-day cycle until dose-limiting toxicities
Maximum Plasma Concentration (Cmax)
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Area Under the Curve, Extrapolated to Infinity (AUC[INF])
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Terminal Half-Life (T-Half)
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Clearance Corrected for Body Surface Area (CL/BSA)
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)
Time frame: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the study
Tumor Response
Time frame: Every other 21-day cycle
Human Anti-cetuximab Antibody (HACA) Response
Time frame: Blood was drawn immediately prior to cetuximab infusions, on a 21-day cycle
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Time frame: Weekly throughout the study and every 4 weeks thereafter
Grade 3-4 Laboratory Abnormalities - Leukopenia
Time frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3-4 Laboratory Abnormalities - Neutropenia
Time frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3-4 Laboratory Abnormalities - Thrombocytopenia
Time frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Grade 3/4 Laboratory Abnormalities - Hypomagnesemia
Time frame: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19770383Trippett TM, Herzog C, Whitlock JA, Wolff J, Kuttesch J, Bagatell R, Hunger SP, Boklan J, Smith AA, Arceci RJ, Katzenstein HM, Harbison C, Zhou X, Lu H, Langer C, Weber M, Gore L. Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: a study of the pediatric oncology experimental therapeutic investigators' consortium. J Clin Oncol. 2009 Oct 20;27(30):5102-8. doi: 10.1200/JCO.2008.20.8975. Epub 2009 Sep 21.
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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
9 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 Cetuximab + Irinotecan in people with Cancer and Refractory Solid Tumor, run by Eli Lilly and Company at 9 sites in United States.
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 2 inclusion and 3 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 24 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 11 Aug 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?
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan (time frame: Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.). 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 NCT00110357, which also lists 1 linked publication.
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 24 Dec 2015.