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A Study of IMC-A12 in Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Parexel
Medidata Solutions
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01007032
First received: November 2, 2009
Last updated: November 5, 2014
Last verified: November 2014
  Purpose

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


Condition Intervention Phase
Tumors
Biological: IMC-A12
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Summary listing of Participants Reporting Treatment-Emergent Adverse Events that received IMC-A12.

  • Maximum concentration (Cmax) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion

  • Area under the Curve (AUC) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Half-life (T1/2) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Drug clearance (CL) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The rate of elimination proportional to the amount of drug in the body


Secondary Outcome Measures:
  • Serum Anti-IMC-A12 Antibody Assessment (immunogenicity) Immunogenicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Screen for the development of circulating antibodies against IMC-A12


Enrollment: 21
Study Start Date: November 2009
Estimated Study Completion Date: March 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-A12
Pts will receive I.V. IMC-A12 every 2 or 3 weeks. A cycle is defined as 6 weeks, with radiological evaluation of tumor response after each cycle. After the 1st cycle, pts with a complete response (CR), PR, or SD will continue to receive IMC-A12 at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met. A minimum of 3 pts will be enrolled in each cohort. The starting dose in Cohort 1 will be 6 mg/kg every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg every 2 weeks) will occur once at least 3 pts in Cohort 1 have completed 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 (as defined above) in Cohort 2. Similarly, pts will be enrolled in Cohort 4 once at least 3 pts have completed once cycle of therapy in Cohort 3; pts in Cohort 4 will receive 20 mg/kg given every 3 weeks.
Biological: IMC-A12
IMC-A12 intravenously
Other Names:
  • Cixutumumab
  • LY3012217

Detailed Description:

Patients in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (I.V.) IMC-A12 every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, patients experiencing a best overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive IMC-A12 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 patients 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 patients in Cohort 1 have completed one cycle of therapy (ie, completed the initial 6 week treatment period or discontinued therapy due to an IMC-A12 -related adverse event [AE]).

Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until all patients have completed one cycle of therapy (as defined above) in Cohort 2. Similarly, patients will be enrolled in Cohort 4 once at least three patients have completed one cycle of therapy in Cohort 3; patients 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. Patients in any cohort who do not complete the first 6 weeks of treatment for reasons other than an IMC-A12 -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 IMC-A12 : 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 patients 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 patients of Cohort 1 (or any cohort) during Cycle 1, three additional patients will be enrolled into that cohort. If no additional DLTs are observed, dose escalation may continue as described above.

If two or more patients in Cohort 1 experience a DLT, six patients will be enrolled into Cohort 1A (receiving 4 mg/kg every 2 weeks). If two or more patients experience a DLT in dose Cohort 3, six patients will be enrolled into dose Cohort 3A (10 mg/kg every 3 weeks). If two or more patients experience a DLT in dose Cohorts 2 or 4, six additional patients 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 patients 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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Solid tumor patient who has been histopathologically or cytologically documented
  • Advanced primary or recurrent solid tumor patient who has not responded to standard therapy or for whom no standard therapy is available
  • The patient has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) guidelines
  • The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)score of 0-1 at study entry
  • The patient is able to provide informed consent
  • The patient is age 20 years or older
  • The patient has a life expectancy of > 3 months
  • The patient 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 patient 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 patient has adequate renal function, as defined by:
  • Serum creatinine ≤ 1.5 mg/dL
  • Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min
  • The patient 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 patient has adequate coagulation function, as defined by an international normalized ratio (INR) ¬ 1.5
  • The patient agrees to use adequate contraception for the duration of study participation and for 12 weeks after the last dose of study therapy.
  • The patient 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 nonapproved monoclonal antibodies, a minimum of 8 weeks must have elapsed
  • The patient is willing to comply with study procedures until the end of therapy

Exclusion Criteria:

  • The patient has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the patient has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
  • The patient 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 patient has elective or planned surgery to be conducted during the trial
  • The patient has documented and/or symptomatic brain or leptomeningeal metastases (patients 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 patient has an uncontrolled intercurrent illness including, but not limited to:
  • Thrombotic or hemorrhagic disorders
  • 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 patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to study entry
  • The patient has experienced any Grade 3/4 gastrointestinal bleeding within 3 months prior to study entry
  • The patient has participated in clinical studies of nonapproved experimental agents or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks prior to study entry for nonapproved monoclonal antibodies
  • The patient has received any previous treatment with agents targeting the IGF-IR, approved or nonapproved
  • The patient 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 patient may have allergies, the patient should be excluded
  • The patient, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
  • The patient has a known alcohol or drug dependency
  • The patient is HBV antigen-, HCV antibody-, or HIV antibody-positive (asymptomatic healthy carriers with detectable HBV-DNA, HCV-RNA may be enrolled into the trial)
  • The patient is assessed as inadequate for the study by the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01007032

Locations
Japan
ImClone Investigational Site
Kashiwa, Japan, 277 8577
Sponsors and Collaborators
Eli Lilly and Company
Parexel
Medidata Solutions
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01007032     History of Changes
Other Study ID Numbers: 13905, 21-1258, CP13-0813, I5A-IE-JAEA
Study First Received: November 2, 2009
Last Updated: November 5, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eli Lilly and Company:
anti-IGF-IR
monoclonal
solid tumor
insulin-like growth factor

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014