A Study of IMC-A12 in Advanced Solid Tumors
Condition: Tumors
MeSH terms: Neoplasms
Intervention: Cixutumumab
Intervention description: Cixutumumab intravenously
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: anti-IGF-IR; monoclonal; solid tumor; insulin-like growth factor

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 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  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

        Exclusion Criteria:

          -  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

          -  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