Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors
Condition: Neoplasms
Intervention: rhuMAb 2C4
Intervention MeSH terms: Pertuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this Phase I study is to test the safety of rhuMAb 2C4 to see what effects
      (good and bad) it has on patients with certain types of cancer, and also to find the highest
      dose of rhuMAb that can be given without causing severe side effects. All study participants
      will be assigned to specific group to evaluate different dosages of rhuMAb 2C4. The study is
      scheduled to run for up to one year depending on how patients respond to the study treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent

          -  Age >=18 years old

          -  ECOG performance status of 0 or 1 (see Appendix F)

          -  Life expectancy of >=12 weeks

          -  Histologically documented, incurable, locally advanced or metastatic solid
             malignancies

          -  Disease progression on or after standard effective therapy or a malignancy for which
             there is no standard therapy

          -  At least one bi-dimensionally measurable lesion (>=2 cm [>=1 cm on spiral CT scan])

          -  HER2-negative status as defined by fluorescence in situ hybridization (FISH) testing
             (only for subjects with breast cancer)

          -  Use of an effective means of contraception for women of childbearing potential

          -  Granulocyte count of >=1500/uL, platelet count of >=100,000/uL, and hemoglobin of >=9
             g/dL

          -  Serum bilirubin less than or equal to the upper limit of normal (ULN) and alkaline
             phosphatase, AST, and ALT <=2.5x ULN (ALT and AST <=5x ULN for subjects with liver
             metastases; alkaline phosphatase <=5x ULN for subjects with liver or bone metastases)

          -  Serum creatinine less than or equal to ULN or creatinine clearance of >=60 mL/min

          -  International normalized ratio (INR) of <1.3 and activated partial thromboplastin time
             (aPTT) of <1.5x ULN

        Exclusion Criteria:

          -  Pleural effusions, ascites, or bone lesions as the only manifestation of the current
             cancer

          -  Symptomatic or untreated brain metastases

          -  Prior chemotherapy, hormonal therapy (except for androgen-deprivation therapy for
             subjects with prostate cancer), radiotherapy, or immunotherapy within 4 weeks of Day 1
             (within 6 weeks for nitrosoureas or mitomycin)

          -  Prior treatment with Herceptin

          -  Prior cumulative doxorubicin dose of >360 mg/m2 or the equivalent

          -  History of other malignancies within 5 years of Day 1 except for adequately treated
             carcinoma in situ of the cervix or basal or squamous cell skin cancer

          -  History of significant cardiac disease, unstable angina, congestive heart failure,
             myocardial infarction, or ventricular arrhythmia requiring medication

          -  Ejection fraction of <50% or below the lower limit of normal determined by ECHO
             (Subjects who are unable to have ejection fraction evaluated by ECHO may have ejection
             fraction evaluated by a MUGA scan, although this must be discussed with the Medical
             Monitor prior to enrollment.)

          -  Active infection requiring IV antibiotics

          -  Uncontrolled hypercalcemia (>11.5 mg/dL)

          -  Clinically important history of liver disease, including viral or other hepatitis,
             current alcohol abuse, or cirrhosis

          -  Known human immunodeficiency virus (HIV) infection

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the subject at high risk from treatment
             complications

          -  Major surgery or significant traumatic injury within 3 weeks of Day 1

          -  Pregnancy or lactation

          -  Inability to comply with study and follow-up procedures