Phase II Study of IMC-A12 in Patients With Mesothelioma Who Have Been Previously Treated With Chemotherapy
Condition: Pleural Mesothelioma; Peritoneal Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: IMC-A12
Intervention description: 20 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Monoclonal Antibody; Pleural Mesothelioma; Peritoneal Mesothelioma

Summary:

      Background:

      Background:

      - IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug
      Administration, is an antibody that is designed to block the effects of a protein called Type
      I Insulin-Like Growth Factor (IGF-1R). IMC-A12 blocks the receptors in cells that respond to
      IGF-1R, which are thought to play an important role in helping cancer cells to grow and
      divide. Researchers are interested in determining whether IMC-A12 is an effective treatment
      for individuals who have mesothelioma that has not responded to standard chemotherapy.

      Objectives:

      - To evaluate the safety and effectiveness of IMC-A12 treatment in individuals with
      mesothelioma who have previously had chemotherapy.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with mesothelioma that has not
      responded to chemotherapy.

      Design:

        -  Eligible participants will be screened with a full physical examination and medical
           history, blood and urine samples, and imaging studies.

        -  Participants will receive IMC-A12 once every 3 weeks (21-day cycle), and will be
           evaluated before the start of each new cycle with blood tests and imaging studies if
           needed.

        -  Treatment cycles will continue for as long as needed, unless severe side effects develop
           or the disease progresses.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Subjects must have histologically confirmed pleural or peritoneal mesothelioma not
             amenable to potentially curative surgical resection. The diagnosis will be confirmed
             by the pathology department / Center for Cancer Research (CCR) / National Cancer
             Institute (NCI).

          2. Patients must have had at least one prior platinum-containing chemotherapy regimen.
             There is no limit to the number of prior chemotherapy regimens received.

          3. Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >
             20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT)
             scan.

          4. Patients must not have had major surgery, radiation therapy, chemotherapy, biologic
             therapy (including any investigational agents), or hormonal therapy (other than
             replacement), within 4 weeks prior to entering the study and must have evidence of
             stable or progressive disease to be eligible.

          5. Age greater than or equal to 18 years. Since mesothelioma is extremely rare in
             children they are excluded from this study.

          6. Life expectancy of greater than 3 months.

          7. Performance status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.

          8. Patients must have adequate organ and marrow function (as defined below).

               -  leukocytes greater than or equal to 3,000/mm^3

               -  absolute neutrophil count greater than or equal to 1,500/mm^3

               -  hemoglobin greater than or equal to 9 g/dL

               -  platelets greater than or equal to 100,000/ mm^3

               -  total bilirubin less than or equal to 1.5 times institutional upper limit of
                  normal (ULN)

               -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase
                  (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT)
                  less than or equal to 3 times institutional ULN

                  (5 times if liver function test (LFT) elevations due to liver metastases)

               -  creatinine less than or equal to 1.5 times institutional ULN

             OR

             - creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
             creatinine

             levels above institutional normal

             Patients may be transfused to obtain a hemoglobin of greater than or equal to 9 g/Dl.

          9. The patient must have fasting serum glucose < 160 mg/dL

         10. The effects of IMC-A12 on the developing human fetus are unknown. For this reason,
             women of child-bearing potential and men must agree to use adequate contraception
             (barrier method of birth control; abstinence) for the duration of study therapy and
             for 3 months after the last dose of IMC-A12. Should a woman become pregnant or suspect
             she is pregnant while participating in this study, she should inform her treating
             physician immediately. While hormonal methods of birth control are effective, we ask
             that female patients who are participating in the study cease hormonal forms of birth
             control, as these methods of birth control (birth control pills, injections, or
             implants) may affect the study drug. Patients must be off hormonal forms of birth
             control for at least 4 weeks prior to initiating the study.

         11. Ability to comply with intravenous administration schedule, and the ability to
             understand and the willingness to sign a written informed consent document.

        Inclusion of Women and Minorities

        Both men and women and members of all races and ethnic groups are eligible for this trial.
        Every effort will be made to recruit women and minorities in this study.

        EXCLUSION CRITERIA:

          1. Patients with symptomatic brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.
             However, patients who have had treatment for their brain metastases and whose brain
             metastatic disease status has remained stable for at least 3 months without steroids
             may be enrolled at the discretion of the principal investigator.

          2. Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes
             mellitus are allowed to participate, provided their blood glucose is below 160 mg/dL
             when fasting and if they are on a stable dietary or therapeutic regimen for this
             condition with their HbA1C of less than 7%.

          3. Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled,
             symptomatic congestive heart failure (American Heart Association (AHA) Class II or
             worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          4. Human immunodeficiency virus (HIV) positive patients with poorly controlled viral
             loads (viral load > 50 copies HIV/ml), and/or acquired immune deficiency syndrome
             (AIDS)-defining illnesses will be excluded due to the possibility that IMC-A12 may
             worsen their condition and the likelihood that the underlying condition may obscure
             the attribution of adverse events with respect to IMC-A12. HIV positive patients with
             mesothelioma not meeting the above criteria can be considered for inclusion in the
             study.

          5. Patients may not be receiving any other investigational agents.

          6. History of another invasive malignancy in the last five years. Adequately treated
             non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix
             will be allowed.

          7. Prior treatment with drugs of the IGF-1R inhibitor class.

          8. Patients with tumor amenable to potentially curative therapy as assessed by the
             investigator. In patients with peritoneal mesothelioma who have had no prior surgery,
             a surgical consultation will be obtained to see if the patient is a candidate for
             debulking surgery.

          9. Pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody
             to IGF-1R with the potential for teratogenic or abortifacient effects. Immunoglobulin
             G (IgG) antibody may also potentially be secreted in milk and therefore breastfeeding
             women should be excluded. Because of the potential of teratogenic or abortifacient
             effects women of childbearing potential and men must agree to use adequate
             contraception (barrier methods) before, during the study and for a period of 3 months
             after the last dose of the investigational agent.

         10. Patients must not be on hormonal forms of birth control or hormone replacement
             therapy, as this may affect the study drug. Patients must be off hormonal forms of
             birth control or hormone replacement therapy for at least 4 weeks prior to initiating
             the study.

         11. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to IMC-A12.