Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy
Condition: Thymoma; Thymic Carcinoma; Thymic Carcinoid; Thymic Neuroendocrine Tumors
MeSH terms: Carcinoma; Neuroendocrine Tumors; Thymoma; Thymus Neoplasms
Intervention: IMC-12
Intervention description: 20 mg/kg intravenously once every three weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Thymic Malignancies; IMC-A12; Insulin-Like Growth Factor

Summary:

      Background:

        -  Cisplatin-containing chemotherapy is the standard of care for advanced thymoma and
           thymic carcinoma that cannot be treated with surgery. New options for treatment are
           necessary in patients with advanced thymoma and thymic carcinoma that have progressed on
           cisplatin-containing therapy.

        -  IMC-A12 is a new (experimental) agent that has not yet been approved by the Food and
           Drug Administration. IMC-A12 blocks the Insulin-like Growth Factor 1 receptor (IGF-1R).
           IGF-1R is found on many types of cancer cells, including cancer of the thymus, and is
           thought to play an important role in helping these cells to grow and divide.

      Objectives:

        -  To determine if IMC-A12 has an effect on tumor growth in patients with cancer of the
           thymus.

        -  To evaluate the safety and tolerability of IMC-A12 in treatment for cancer of the
           thymus.

      Eligibility:

      - Individuals older than 18 years of age who have cancer of the thymus (thymoma, thymic
      carcinoma, or thymic carcinoid tumors) that has progressed in spite of standard treatment.

      Design:

        -  Treatment will take place in 21-day cycles. Patients will receive one dose of IMC-A12
           intravenously once every 3 weeks at the Clinical Center. During the Clinical Center
           visits, researchers will perform study tests and procedures to see how the study drugs
           are affecting the body.

        -  Patients will undergo a number of tests and procedures during the treatment cycle,
           including physical examinations, blood and urine samples for standard tests, imaging
           studies (ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scans)
           to evaluate tumor growth, and blood and urine samples to evaluate the amount of IMC-A12
           in the body.

        -  Patients may continue to take the drug as long as there are no adverse side effects and
           as long as the tumor does not grow.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Histologically confirmation of invasive recurrent or metastatic thymoma or thymic
             carcinoma by the pathology department / Center for Cancer Research (CCR) / National
             Cancer Institute (NCI), or the pathology department of participating institutions.

          -  Patients must have had at least one prior platinum-containing chemotherapy regimen.
             There is no limit to the number of prior chemotherapy regimens received. Progressive
             disease should have been documented before entry into the study.

          -  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
             greater than 20 mm with conventional techniques or as greater than 10 mm with spiral
             CT scan. See section 11 for the evaluation of measurable disease.

          -  Target lesions cannot be selected within previously irradiated areas, if not newly
             arising or clearly progressing after irradiation as proven by repeat scanning.

          -  Patients must have recovered from toxicity related to prior therapy to at least to
             grade 1 (defined by CTCAE 3.0 until December 31, 2010, and by CTCAE 4.0 beginning
             January 1, 2011) and 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.

          -  Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes
             which often accompany thymic malignancies are allowed. Inhaled steroids are also
             allowed. However since steroids might occasionally induce responses in thymic
             malignancies patients should be on a stable dose of steroids for greater than or equal
             to 8 weeks before enrollment in order not to confound the efficacy assessment.

          -  Age greater than 18 years. Because no dosing or adverse event data are currently
             available on the use of IMC-A12 in patients less than 16 years of age, children are
             excluded from this study but will be eligible for future pediatric phase 1
             single-agent trials.

          -  Life expectancy of greater than 3 months.

          -  Performance status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.

          -  Patients must have adequate organ and marrow function (as defined below). Patients
             must have returned to baseline or grade 1 from any acute toxicity related to prior
             therapy:

               -  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 the institutional upper limit of
                  normal (ULN)

               -  aspartate aminotransferase (AST)(SGOT)/alanine aminotransferase (ALT)(SGPT) less
                  than or equal to 3 times the institutional ULN

                  (5x if LFT elevations due to liver metastases)

               -  creatinine less than or equal to 1.5 times the 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 9.0.

          -  The patient must have fasting serum glucose less than 120 mg/dL or below the
             institutional ULN

          -  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
             (hormonal or 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.

          -  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:

          -  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.

          -  Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes
             mellitus are allowed to participate, provided their blood glucose is within the normal
             range (fasting less than 120 mg/dL or below institutional upper limit of normal) and
             if they are on a stable dietary or therapeutic regimen for this condition.

          -  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.

          -  Human Immunodeficiency virus (HIV) positive patients with poorly controlled viral
             loads (viral load greater than 50 copies HIV/ml), and/or 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 thymic malignancies not meeting
             the above criteria can be considered for inclusion in the study.

          -  Patients may not be receiving any other investigational agents.

          -  History of another invasive malignancy in the last five years. Adequately treated
             non-invasive, non-melanoma skin cancers, in situ carcinoma of the cervix, and
             surgically-removed papillary thyroid cancer will be allowed.

          -  Prior treatment with drugs of the IGF-1R inhibitor class.

          -  Patients with tumor amenable to potentially curative therapy as assessed by the
             investigator.

          -  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. IgG antibody
             may also potentially be secreted in milk and therefore breastfeeding women should be
             excluded.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to IMC-A12.