Advanced Solid TumorsPhase 1NCT00785538
A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is Available
A Phase 1 study testing IMC-A12 in people with Advanced Solid Tumors, run by Eli Lilly and Company at 3 sites in United States.
Trial summary
The purpose of this study is to determine if IMC-A12 is safe for participants, and also to determine the best dose of IMC-A12 to give to participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- IMC-A12
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2005to Jan 2011
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathologically-documented, measurable, advanced primary or recurrent solid tumors that no longer respond to standard therapy or for which no standard therapy is available.
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2 at study entry
- Able to provide written informed consent
- Life expectancy of >3 months
- Adequate hematologic functions, as defined by: absolute neutrophil count (ANC) ≥1500/cubic millimeter (mm³), hemoglobin level ≥10 grams/deciliter (gm/dL), platelet count ≥100,000/mm³
- Adequate hepatic function, as defined by: total bilirubin level ≤1.5 x the upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤2.5 x the ULN or ≤5 x the ULN if known liver metastases
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- Adequate renal function, as defined by a serum creatinine level ≤1.5 x the ULN
- Ejection fraction within the normal institutional limits
- Use of effective contraception per institutional standard, if procreative potential exists
- At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, prior radiation therapy (palliative radiation therapy is allowed), an open biopsy, or a significant traumatic injury to allow for adequate recovery. Ongoing side effects due to these agents must be ≤Grade 2 prior to entering the study.
- At least 6 weeks must have elapsed from nitrosoureas, mitomycin C, or monoclonal antibody [not targeting the insulin-like growth factor receptor (IGFR)] therapy to allow for adequate recovery. Ongoing side effects due to these agents must be ≤Grade 2 prior to entering the study.
- Accessible for treatment and follow-up. Participants enrolled in this trial must be treated at the participating center.
Who cannot join
- Any concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix. Participants with a previous malignancy but without evidence of disease for ≥3 years will be allowed to enter the trial.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, angioplasty, stenting or myocardial infarction within 6 months, uncontrolled hypertension, clinically significant cardiac arrhythmia, psychiatric illness/social situations that would compromise participant safety or limit compliance with study requirements, participants with symptomatic brain metastases
- Serious or nonhealing active wound, ulcer or bone fracture
- Know human immunodeficiency virus (HIV)-positive
- History of hemorrhagic or thrombotic disorder within 9 months
- Proteinuria ≥1+ by routine urinalysis (participants with a protein value of ≤500 milligrams (mg) confirmed by a 24-hour urine collection are eligible)
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- Pregnant [confirmed by serum beta human chorionic gonadotropin (βHCG)] or breast feeding
- History of prior treatment with other agents specifically targeting IGFRs
- Known diabetes
- Inability or unwillingness to interrupt steroidal or hormonal therapy for the duration of treatment with IMC-A12
- Positive anti-IMC-A12 antibody response
- History of allergic reactions to monoclonal antibodies or other therapeutic proteins
- 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
3 sites in 1 country.
United States3 sites
ImClone Investigational Site
Detroit, Michigan, 48201
ImClone Investigational Site
Scottsdale, Arizona, 85258
ImClone Investigational Site
Seattle, Washington, 98109
About this study
Official title: Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available
The purpose of this study is to determine if IMC-A12 is safe for participants, and also to determine the best dose of IMC-A12 to give to participants.
Read the detailed description
The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered weekly in participants with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available
- Conditions
- Advanced Solid Tumors
- Being tested
- IMC-A12
- Keywords
- Tumors, Antibodies, Monoclonal
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 1
3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 2
6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 3
10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 4
15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 5
21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
IMC-A12Biological
Also called Cixutumumab, LY3012217
Cohort 6
27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
| Study group | Role | What they receive |
|---|---|---|
| IMC-A12 | Experimental | All participants will receive intravenous (I.V.) infusions of IMC-A12, with the dose depending on which cohort they are enrolled into. A minimum of three participants will be enrolled in each cohort. When all participants complete a cohort, dose escalation to the next cohort will occur. Receives: Biological: IMC-A12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) or Deaths
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Measured: Enrollment to study completion up to 215 weeks
Maximum Tolerated Dose (MTD)
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.
Measured: 6 weeks
Secondary outcomes (8)
Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Half-Life (t1/2) of IMC-A12 Following Multiple Doses
Half-Life (t1/2) is the time measured for the plasma concentration of the drug to decrease by one half. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses
CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
Measured: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
Analysis was not performed due to lack of available assay.
Measured: Before the last infusion of each treatment cycle
Number of Participants With Best Overall Response
Stable Disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD). PR and PD were assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants with a global deterioration of their health status requiring discontinuation of treatment without objective evidence of disease progression at that time were to be reported as "symptomatic deterioration"
Measured: Enrollment to study completion up to 215 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2008 (estimated)
- Study startOct 2005
- Primary completionJan 2011
- Study completionJan 2011
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 Advanced Solid TumorsStudies 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT00785538
- Sponsor's protocol ID
- 13932
- Other IDs
- CP13-0501, I5A-IE-JAEH
- Status last verified
- Dec 2018
- First submitted
- 4 Nov 2008
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Higano CS, Berlin J, Gordon M, LoRusso P, Tang S, Dontabhaktuni A, Schwartz JD, Cosaert J, Mehnert JM. Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):450-62. doi: 10.1007/s10637-015-0217-7. Epub 2015 Mar 7.
PubMed 25749986
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available
- ClinicalTrials.gov ID
- NCT00785538
- Acronym / sponsor ID
- 13932
- Conditions
- Advanced Solid Tumors
- Keywords
- Tumors, Antibodies, Monoclonal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Oct 2005
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 5 Nov 2008 (estimated)
- Results
- Posted 22 Oct 2018
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 study is to determine if IMC-A12 is safe for participants, and also to determine the best dose of IMC-A12 to give to participants.
Detailed description
The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered weekly in participants with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMC-A12 | Experimental | Biological: IMC-A12All participants will receive intravenous (I.V.) infusions of IMC-A12, with the dose depending on which cohort they are enrolled into. A minimum of three participants will be enrolled in each cohort. When all participants complete a cohort, dose escalation to the next cohort will occur. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histopathologically-documented, measurable, advanced primary or recurrent solid tumors that no longer respond to standard therapy or for which no standard therapy is available.
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2 at study entry
- Able to provide written informed consent
- Life expectancy of >3 months
- Adequate hematologic functions, as defined by: absolute neutrophil count (ANC) ≥1500/cubic millimeter (mm³), hemoglobin level ≥10 grams/deciliter (gm/dL), platelet count ≥100,000/mm³
Key exclusion criteria (13 listed)
- Any concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix. Participants with a previous malignancy but without evidence of disease for ≥3 years will be allowed to enter the trial.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, angioplasty, stenting or myocardial infarction within 6 months, uncontrolled hypertension, clinically significant cardiac arrhythmia, psychiatric illness/social situations that would compromise participant safety or limit compliance with study requirements, participants with symptomatic brain metastases
- Serious or nonhealing active wound, ulcer or bone fracture
- Know human immunodeficiency virus (HIV)-positive
- History of hemorrhagic or thrombotic disorder within 9 months
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 |
|---|---|---|
| IMC-A12Also: Cixutumumab, LY3012217Cohort 1 3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
| IMC-A12Also: Cixutumumab, LY3012217Cohort 2 6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
| IMC-A12Also: Cixutumumab, LY3012217Cohort 3 10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
| IMC-A12Also: Cixutumumab, LY3012217Cohort 4 15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
| IMC-A12Also: Cixutumumab, LY3012217Cohort 5 21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
| IMC-A12Also: Cixutumumab, LY3012217Cohort 6 27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period. | Biological | IMC-A12 |
Primary outcome
Number of Participants With Adverse Events (AEs) or Deaths
Time frame: Enrollment to study completion up to 215 weeks
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Maximum Tolerated Dose (MTD)
Time frame: 6 weeks
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.
8 secondary outcomes
Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Half-Life (t1/2) of IMC-A12 Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses
Time frame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
Time frame: Before the last infusion of each treatment cycle
Number of Participants With Best Overall Response
Time frame: Enrollment to study completion up to 215 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25749986Higano CS, Berlin J, Gordon M, LoRusso P, Tang S, Dontabhaktuni A, Schwartz JD, Cosaert J, Mehnert JM. Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):450-62. doi: 10.1007/s10637-015-0217-7. Epub 2015 Mar 7.
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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 IMC-A12 in people with Advanced Solid Tumors, run by Eli Lilly and Company at 3 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 12 inclusion and 13 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 8 Jan 2019. 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 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 22 Oct 2018). 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 With Adverse Events (AEs) or Deaths (time frame: Enrollment to study completion up to 215 weeks). 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 NCT00785538, 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 8 Jan 2019.