Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma
Condition: Pleural Malignant Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: GC1008
Intervention description: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Subjects who have pleural malignant mesothelioma

Summary:

      This study is being conducted to evaluate the overall safety and effectiveness of an
      investigational drug, GC1008, in patients with mesothelioma. An investigational drug is one
      that has not been approved by the FDA. Approximately 40 people will be enrolled on this study
      at the University of Pennsylvania (Main Institution/Coordinating Site) and the University of
      Chicago (Participating Institution). We expect about 20 subjects to be enrolled at each
      institution.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically [histologically or cytologically] documented pleural malignant
             mesothelioma.

        Patients must have had at least one, but no more than two prior systemic therapies, at
        least one of which contained pemetrexed.

          -  Documented progressive disease evaluable by Modified RECIST criteria. [Progressive
             symptoms after 1st line therapy in the absence of objective progression are acceptable
             as a criterion for enrollment]. Patients who have had previous extrapleural
             pneumonectomy and disease recurrence will be eligible if they have no other exclusion
             criteria.

          -  ECOG Performance status of 0 or 1.

          -  Greater or equal to 18 years of age.

          -  Male and female patients of child-producing potential must agree to use effective
             contraception while enrolled on study and receiving the experimental drug, and for at
             least 3 months after the last treatment.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 1 week prior to beginning treatment on this trial.

          -  Must be able and willing to give written informed consent. Patients may not be
             consented by a durable power of attorney.

          -  Serum albumin greater or equal to 2.5

          -  Adequate organ function

          -  Patients must have negative tests for human immunodeficiency virus (HIV) and for
             hepatitis viruses B and C (antibody and/or antigen) unless the result is consistent
             with prior vaccination or prior infection with full recovery.

          -  At the time of enrollment, patients must be greater than 3 weeks since major surgery,
             radiotherapy, chemotherapy (greater or equal to 6 weeks if they were treated with a
             nitrosourea, mitomycin or monoclonal antibody), immunotherapy, or biotherapy/targeted
             therapies and recovered from the toxicity of prior treatment to less than or equal to
             Grade 1, exclusive of alopecia. Concurrent non-protocol cancer therapy is not
             permitted. (In patients who received long acting agents, a treatment free interval of
             2 half lives should be considered.) Note: Although a patient can be entered by these
             criteria, if a patient is less than 3-6 months from radiotherapy or talc pleurodesis,
             FDG-PET scanning will not be useful. 12).

        Exclusion Criteria:

          -  Known central nervous system (CNS) metastases, meningeal carcinomatosis, malignant
             seizures, or a disease that either causes or threatens neurologic compromise (e.g.,
             unstable vertebral metastases).

          -  Presence of pericardial effusion

          -  Rapidly re-accumulating, symptomatic malignant pleural effusions status-post
             thoracentesis or pleural catheter insertion that requires immediate mechanical or
             chemical pleurodesis for adequate palliation.

          -  Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or use
             of anti-coagulation therapy (including lovenox, warfarin, or anti platelet agents such
             as aspirin [with the exception of low dose ASA ~ 81 mg/d] , clopidogrel, ticlopidine,
             dipyridamole, and other agents used to induce long-acting platelet dysfunction).
             Patients with a history of deep venous thrombosis may participate if successfully
             treated, completely resolved, and no treatment has been given for greater than 4
             months.

          -  Pregnant or nursing women, due to the unknown effects of GC1008 on the developing
             fetus or newborn infant.

          -  Other active invasive malignancy requiring ongoing therapy.

          -  Patients with an organ transplant, including those that have received an allogeneic
             bone marrow transplant.

          -  Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks
             if the treatment was with a long-acting agent such as a monoclonal antibody).

          -  Patients on immunosuppressive therapy

          -  Significant or uncontrolled medical illness, such as congestive heart failure (CHF),
             myocardial infarction, symptomatic coronary artery disease, significant ventricular
             arrhythmias within the last 6 months, or significant pulmonary dysfunction.

        Patients with a remote history of asthma or active mild asthma may participate.

          -  Active infection, including active herpes zoster, as well as unexplained fever
             (temperature 38.1C), or antibiotic therapy within 1 week prior to enrollment.

          -  Systemic autoimmune disease (e.g., systemic lupus erythematosus, active rheumatoid
             arthritis, etc.).

          -  Positive stool fecal occult blood test (patients who are positive will need a standard
             GI work-up consisting of an Esophagogastroduodenoscopy (EGD) and Colonoscopy) prior to
             enrollment to rule out possible reasons for bleeding. A patient will be eligible with
             negative results for both exams.

          -  Active GI bleeding within past 5 years other than due to benign anorectal causes such
             as hemorrhoids, fissures and stricture.

          -  A known allergy to any component of GC1008.

          -  Patients who, in the opinion of the Investigator, have significant medical or
             psychosocial problems that warrant exclusion.