AzTrials
AzTrials

Colorectal CancerPhase 2NCT00503685

Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFR Therapy

A Phase 2 study testing IMC-A12 and cetuximab in people with Colorectal Cancer, run by Eli Lilly and Company at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Participants with metastatic Colorectal Cancer (mCRC) who have progressed on a prior Anti-epidermal growth factor receptor (EGFR) regimen randomized to receive IMC-A12 monotherapy or combination therapy with cetuximab to assess response, survival, durations of response, safety and tolerability as well as… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
IMC-A12 and cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
4 sitesUnited States
Study dates
Jun 2007to Mar 2009
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

  • The participant has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies
  • The participant has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring ≥ 2 centimeter (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
  • The participant has clinical documentation of disease progression during treatment or within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or planned treatment break will not be regarded as adequate evidence of disease progression and such participants will not be eligible for this trial
  • The participant has received at least one prior standard and/or investigational regimen for metastatic disease
  • The participant is age ≥ 18 years
  • The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 (Karnofsky ≥ 80%
Show all 16Show fewer
  • The participant has adequate hematologic function as defined by an absolute neutrophil count ≥ 1500/microliter (μL), hemoglobin ≥ 9 grams/deciliter (g/dL), and a platelet count ≥ 100,000/μL
  • The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
  • The participant has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have an INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or invading the rectal lumen, or known varices)
  • The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliters/minute (mL/min) for participants with creatinine levels above the ULN, as well as urine protein ≤ 1+ on urine dipstick or routine urinalysis [(UA), if urine dipstick/routine UA indicates ≥ 2+ protein, a 24-hour urine collection for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study]
  • The participant has fasting serum glucose < 120 milligrams/deciliter (mg/dL) or below the ULN
  • The participant has a life expectancy of > 3 months
  • Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • The participant has the ability to understand and the willingness to sign a written informed consent document
  • The participant has a tumor that is K-ras wild-type (absence of mutations at codon 12 or 13, as determined by the DxS K-ras Mutation Kit [polymerase chain reaction (PCR)-based analysis]).
  • The participant experienced either a confirmed partial response or stable disease of ≥ 24 weeks duration during prior treatment with a cetuximab- or panitumumab-containing regimen except for participants with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) promoter polymorphism, for example, Gilbert syndrome, confirmed by genotyping or Invader®UGT1A1 Molecular Assay prior to enrollment. Participants enrolled with Gilbert Syndrome must have a total bilirubin ≤ 3 x ULN. If the participant has liver metastases, total bilirubin must be ≤ 3 x ULN.

Who cannot join

  • The participant has received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 3.0 grade ≤ 2.
  • The participant is receiving any other investigational agent(s).
  • The participant has a history of treatment with other agents targeting the insulin-like growth factor receptor (IGFR).
  • The participant has known brain or leptomeningeal metastases.
  • The participant has a history of primary central nervous system tumors, seizures not well controlled with standard medical therapy, or history of stroke within 6 months prior to randomization.
  • The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12 (cixutumumab).
Show all 12Show fewer
  • The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.
  • The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • The participant is pregnant or lactating.
  • The participant is known to be positive for infection with the human immunodeficiency virus.
  • The participant is receiving therapy with immune modulators such as cyclosporine or tacrolimus.
  • The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • ImClone Investigational Site

    Buffalo, New York, 14263

  • ImClone Investigational Site

    Los Angeles, California, 90095

  • ImClone Investigational Site

    New Haven, Connecticut, 06520

  • ImClone Investigational Site

    New York, New York, 10021

Other trials in United States

About this study

Official title: A Randomized Phase 2 Clinical Trial of IMC-A12, as a Single Agent or in Combination With Cetuximab, in Patients With Metastatic Colorectal Cancer With Disease Progression on Prior Anti-EGFR Therapy

Participants with metastatic Colorectal Cancer (mCRC) who have progressed on a prior Anti-epidermal growth factor receptor (EGFR) regimen randomized to receive IMC-A12 monotherapy or combination therapy with cetuximab to assess response, survival, durations of response, safety and tolerability as well as pharmacodynamics of IMC-A12 and cetuximab

Being tested
IMC-A12, cetuximab
Keywords
Metastatic Colorectal Cancer with Disease Progression, Failed prior to Anti-EGFr Therapy
Medical subject headings
Colorectal 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

    10 milligrams/kilogram (mg/kg) intravenous infusion every 2 weeks.

  • cetuximabBiological

    Also called Erbitux®

    Participants will receive cetuximab 500 milligrams/square meter (mg/m²) intravenous over 2 hours every 2 weeks.

Study groups in NCT00503685
Study groupRoleWhat they receive
IMC-A12ExperimentalAdministered every 2 weeks
Receives: Biological: IMC-A12
IMC-A12 + cetuximabExperimentalAdministered every 2 weeks
Receives: Biological: IMC-A12; Biological: cetuximab
IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]ExperimentalParticipants who have experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression are enrolled in this arm.
Receives: Biological: IMC-A12; Biological: cetuximab

What is being measured

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

  1. Percentage of Participants With Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)]

    ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

    Measured: Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

Secondary outcomes (12)

  1. Progression-Free Survival (PFS)

    PFS was defined as the duration from the date of randomization/treatment to the date of PD or death from any cause. PD was determined using RECIST criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. Participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last tumor assessment prior to the cutoff date. Participants who began a new antitumor treatment before evidence of PD were categorized as PD.

    Measured: Randomization/treatment to measured PD up to 28.3 weeks

  2. Overall Survival (OS)

    OS is defined as the duration from the date of randomization/treatment to the date of death from any cause. Participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.

    Measured: Randomization/treatment to date of death from any cause up to 26.9 months

  3. Duration of Stable Disease (SD)

    The duration of SD is measured from the date of randomization/treatment until the date of PD. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. RECIST criteria version 1.0 was used to asses PR and PD. 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 who had no PD or death at the time of the data inclusion cutoff, duration of SD was censored at their last tumor assessment prior to the cutoff date.

    Measured: Time from randomization/treatment to first date of PD up to 28.3 weeks

  4. Duration of Overall Response

    The duration of overall response (CR or PR) was defined as the time from first objective status assessment of CR or PR to the first time of PD or death due to any cause. CR, PR and PD were determined using RECIST criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions; PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants with CR or PR who had no PD or death at the time of the data inclusion cutoff, the duration of overall response was censored at their last tumor assessment prior to the cutoff date. Duration of overall response was not analyzed due to low number of participants with CR or PR.

    Measured: Time of response to time of measured PD or death up to 161 days

  5. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

    Data presented are the number of participants who experienced nonserious adverse events (AEs) during the study including the 30-day follow-up. A summary of serious AEs (SAEs) and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

    Measured: Randomization/treatment up to 26.9 months

  6. Number of Participants Reporting Treatment-Emergent Severe Adverse Events

    Data presented are the number of participants who experienced serious adverse events (SAEs) or death 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 Events module.

    Measured: Randomization/treatment up to 26.9 months

  7. Maximum Concentration (Cmax)

    Measured: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

  8. Minimum Concentration (Cmin)

    Measured: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

  9. Area Under Serum Concentration (AUC)

    Measured: Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

  10. Percentage of Participants With Complete Response (CR) or Partial Response (PR, Response Rate) in Participants With Kirsten Rat Sarcoma (K-ras) Mutations

    The response rate in participants with K-ras mutations was not collected for analysis.

    Measured: Treatment up to 26.9 months

  11. Expression of Type I Insulin-Like Growth Factor Receptors (IGF-IR)

    Measured: Randomization/treatment up to 26.9 months

  12. Expression of IGF Binding Proteins (IGFBP2, IGFBP3)

    Measured: Randomization/treatment up to 26.9 months

Timeline

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

  1. First posted19 Jul 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionMar 2009
  4. Study completionMar 2009

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00503685
Sponsor's protocol ID
13936
Other IDs
CP02-0657, CP13-0605, I5A-IE-JAEL
Status last verified
May 2018
First submitted
17 Jul 2007
Last updated
6 Jun 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IMC-A12 and cetuximab in people with Colorectal Cancer, run by Eli Lilly and Company at 4 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 16 inclusion and 12 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 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 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 6 Jun 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?

Percentage of Participants With Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)] (time frame: Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks). 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 NCT00503685.

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 Jun 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT00503685 | AzTrials