A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is Available
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: IMC-A12; IMC-A12; IMC-A12; IMC-A12; IMC-A12; IMC-A12
Intervention description: Cohort 1
3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.; Cohort 2
6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.; Cohort 3
10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.; Cohort 4
15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.; Cohort 5
21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.; Cohort 6
27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tumors; Antibodies, Monoclonal

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  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.

        Exclusion Criteria:

          -  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)

          -  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.