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TumorsPhase 1NCT01007032

A Study of IMC-A12 in Advanced Solid Tumors

A Phase 1 study testing Cixutumumab in people with Tumors, run by Eli Lilly and Company at 1 site in Japan.

Completed

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

Official record
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Trial summary

In this study, participants will initially receive intravenous (IV) cixutumumab (IMC-A12) every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing a best overall response of complete response, partial response, or stable disease will continue to receive cixutumumab at… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Tumors
What is being tested?
Cixutumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteJapan
Study dates
Nov 2009to Apr 2015
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

  • Solid tumor participant who has been histopathologically or cytologically documented
  • Advanced primary or recurrent solid tumor participant who has not responded to standard therapy or for whom no standard therapy is available
  • The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) guidelines
  • The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS)score of 0-1 at study entry
  • The participant is able to provide informed consent
  • The participant is age 20 years or older
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  • The participant has a life expectancy of > 3 months
  • The participant has adequate hematologic function, as defined by:
  • An absolute neutrophil count (ANC) ≥ 1500/m3 or /μL
  • A hemoglobin ≥ 10 g/dL; and
  • A platelet count ≥ 100,000/mm3 or /μL
  • The participant has adequate hepatic function, as defined by:
  • Total bilirubin ≤ 1.8 mg/dL
  • Aspartate transaminase (AST) ≤ 2.5 times the upper limit of site-specific normal ranges (five times in case of liver metastasis)
  • Alanine transaminase (ALT) ≤ 2.5 times the upper limit of site-specific normal ranges (five times in case of liver metastasis)
  • The participant has adequate renal function, as defined by:
  • Serum creatinine ≤ 1.5 mg/dL
  • Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min
  • The participant has fasting blood sugar < 120 mg/dL or below the institutional upper limit of normal (ULN) before study entry (one retest of an elevated level is permitted at the discretion of the investigator)
  • The participant has adequate coagulation function, as defined by an international normalized ratio (INR) ¬ 1.5
  • The participant agrees to use adequate contraception for the duration of study participation and for 12 weeks after the last dose of study therapy.
  • The participant has adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with unapproved monoclonal antibodies, a minimum of 8 weeks must have elapsed
  • The participant is willing to comply with study procedures until the end of therapy

Who cannot join

  • The participant has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the participant has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
  • The participant has undergone major surgery (eg,laparotomy, thoracotomy,removal of organ(s)) within 28 days prior to study entry, or subcutaneous venous access device placement within 7 days prior to study entry
  • The participant has elective or planned surgery to be conducted during the trial
  • The participant has documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable (no symptoms during the 4 weeks prior to enrollment) with an assessment that no further treatment (radiation, surgical excision, or administration of steroids) is required are permitted to enter the study)
  • The participant has an uncontrolled intercurrent illness including, but not limited to:
  • Thrombotic or hemorrhagic disorders
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  • Gross hemoptysis (approximately one-half a teaspoon)
  • Ongoing or active infection requiring systemic antibiotic treatment
  • Congestive heart failure (Class III or IV per the New York Heart Association classification for heart disease)
  • Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
  • Uncontrolled hypertension (systolic blood pressure > 150 mm Hg, diastolic blood pressure > 95 mm Hg)
  • Cardiac arrhythmia requiring treatment (NCICTCAE Version 3.0 Grade 3), or asymptomatic sustained ventricular tachycardia
  • Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE Version 3.0); or
  • Any other serious uncontrolled medical disorder(s) in the opinion of the investigator
  • The participant has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to study entry
  • The participant has experienced any Grade 3/4 gastrointestinal bleeding within 3 months prior to study entry
  • The participant has participated in clinical studies of unapproved experimental agents or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks prior to study entry for unapproved monoclonal antibodies
  • The participant has received any previous treatment with agents targeting the insulin-like growth factor hormone (IGF-IR), approved or unapproved
  • The participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
  • The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
  • The participant has a known alcohol or drug dependency
  • The participant is Hepatitis B Virus (HBV) antigen-, Hepatitis C Virus (HCV) antibody-, or HIV antibody-positive (asymptomatic healthy carriers with detectable HBV-DNA, HCV-RNA may be enrolled into the trial)
  • The participant is assessed as inadequate for the study by the investigator

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • ImClone Investigational Site

    Kashiwa, 277 8577

Other trials in Japan

About this study

Official title: A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-A12 Administered Every 2 Weeks or Every 3 Weeks to Japanese Patients With Advanced Solid Tumors

In this study, participants will initially receive intravenous (IV) cixutumumab (IMC-A12) every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing a best overall response of complete response, partial response, or stable disease will continue to receive cixutumumab at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met. Participants will be enrolled at one study center, located in the National Cancer Center Hospital - East, Kashiwa, Japan. Approximately 20-30 participants are anticipated.

Read the detailed description

Participants in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (IV) cixutumumab every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing a best overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive cixutumumab at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met.

A minimum of three participants will be enrolled in each cohort. The starting dose in Cohort 1 will be 6 mg/kg, administered every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg administered every 2 weeks) will occur once at least three participants in Cohort 1 have completed one cycle of therapy (ie, completed the initial 6 week treatment period or discontinued therapy due to an cixutumumab - related adverse event [AE]).

Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until all participants have completed one cycle of therapy (as defined above) in Cohort 2. Similarly, participants will be enrolled in Cohort 4 once at least three participants have completed one cycle of therapy in Cohort 3;participants in Cohort 4 will receive 20 mg/kg administered every 3 weeks. Toxicity data for each cohort will be reviewed prior to any dose escalation. No intrapatient dose escalation is permitted. Participants in any cohort who do not complete the first 6 weeks of treatment for reasons other than an cixutumumab-related toxicity will be replaced.

A dose-limiting toxicity (DLT) is defined as one of the following events, if considered by the investigator to be definitely, probably, or possibly related to cixutumumab: Grade 4 neutropenia lasting > 7 days; Grade 4 anemia; Grade ≥ 3 thrombocytopenia; Grade ≥ 3 neutropenia associated with fever; Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality and Grade 3 hyperglycemia; Grade 4 hyperglycemia; and/or Grade 4 or uncontrollable hypertension.

If three participants complete the first 6-week cycle (according to the definition outlined above) with no DLTs, dose escalation to Cohort 2 may proceed. If one DLT is observed in the initial three participants of Cohort 1 (or any cohort) during Cycle 1, three additional participants will be enrolled into that cohort. If no additional DLTs are observed, dose escalation may continue as described above.

If two or more participants in Cohort 1 experience a DLT, six participants will be enrolled into Cohort 1A (receiving 4 mg/kg every 2 weeks). If two or more participants experience a DLT in dose Cohort 3, six participants will be enrolled into dose Cohort 3A (10 mg/kg every 3 weeks). If two or more participants experience a DLT in dose Cohorts 2 or 4, six additional participants will be enrolled into the previous cohort (Cohort 1 or Cohort 3, respectively), and the previous cohort will be considered the maximum tolerated dose for that dosing schedule. If two or more participants in any cohort experience a DLT on Week 7 or beyond (after Cycle 1), the data will be reviewed and enrollment may be suspended. The Sponsor and Principal Investigator, with reference to the review of the Independent Data Safety Evaluation Committee (established in a separate document), will determine whether enrollment should resume.

Conditions
Tumors
Being tested
Cixutumumab
Keywords
anti-IGF-IR, monoclonal, solid tumor, insulin-like growth factor
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CixutumumabBiological

    Also called IMC-A12, LY3012217

    Cixutumumab intravenously

Study groups in NCT01007032
Study groupRoleWhat they receive
CixutumumabExperimentalParticipants receive IV cixutumumab every 2 or 3 weeks. A cycle equals 6 weeks, with radiological evaluation of tumor response after each cycle. After 1st cycle, pts with a complete response (CR), PR, or SD continue to receive cixutumumab cohort dose and schedule disease progression. 3 pts enroll in each cohort. Starting dose in Cohort 1 is 6 mg/kg every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg every 2 weeks) occurs at least 3 pts in Cohort 1 completes 1 cycle of therapy. Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until at least 3 pts have completed one cycle of therapy in Cohort 2. Pts enroll in Cohort 4 once at least 3 pts have completed once cycle of therapy in Cohort 3; pts in Cohort 4 receive 20 mg/kg every 3 weeks.
Receives: Biological: Cixutumumab

What is being measured

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

  1. Summary Listing of Percentage of Participants Reporting Treatment-Emergent Adverse Events

    A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

    Measured: Up To 63 Months

  2. Number of Participants With a Dose Limiting Toxicity (DLT)

    DLTs were defined as any cixutumumab-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events (reported in the subsequent Primary Outcome Measure).

    Measured: First Dose Up to 6 Weeks

  3. Pharmacokinetics (PK): Maximum Concentration (Cmax)

    Measured: Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

  4. PK: Area Under the Curve From Zero to Infinity AUC(0-∞)

    Measured: Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

  5. PK: Area Under Concentration Versus Time Curve During One Dosing Interval (AUCtau)

    Measured: Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

  6. Half-life (t1/2)

    Measured: Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 hours) Following End of Infusion

  7. Drug Clearance (CL)

    Measured: Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 hours) Following End of Infusion

Secondary outcomes (2)

  1. Number of Participants With Serum Anti-Cixutumumab Antibody Assessment Immunogenicity

    No participants were analyzed for the development of circulating positive anti-cixutumumab antibodies due to no assay available.

    Measured: 6 months

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

    Response defined per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions.

    Measured: From the First Dose up to 32 Months

Timeline

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

  1. First posted3 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionDec 2012
  4. Study completionApr 2015

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 1
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01007032
Sponsor's protocol ID
13905
Other IDs
21-1258, CP13-0813, I5A-IE-JAEA
Status last verified
Oct 2018
First submitted
2 Nov 2009
Last updated
27 Feb 2019
Data monitoring committee
Yes

Publications

  • Doi T, Shitara K, Kojima T, Yoshino T, Dontabhaktuni A, Rebscher H, Tang S, Cosaert J, Ohtsu A. A phase I study evaluating cixutumumab, a type 1 insulin-like growth factor receptor inhibitor, given every 2 or 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1253-62. doi: 10.1007/s00280-016-3041-7. Epub 2016 Apr 30.

    PubMed 27139036

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cixutumumab in people with Tumors, run by Eli Lilly and Company at 1 site 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 23 inclusion and 23 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 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 27 Feb 2019). 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?

Summary Listing of Percentage of Participants Reporting Treatment-Emergent Adverse Events (time frame: Up To 63 Months). The study lists 7 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 NCT01007032, 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 27 Feb 2019.

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