Phase I/II Study to Evaluate the Efficacy and Safety of a Combination Chemotherapy
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: Bortezomib 1.3 mg/m2; Bortezomib 1.6 mg/m2; Bortezomib 1.8 mg/m2; Carboplatin AUC 6; Bevacizumab; Taxotere
Intervention description: Level I (every 21 day cycle, D8), 1.3 mg/m2:
Day 1: bevacizumab 15 mg/kg ,carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.3 mg/m2 Day 8 : bortezomib 1.3 mg/m2
Level II (every 21 day cycle):
Day 1: bevacizumab 15 mg/kg, carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.6 mg/m2 Day 8 : bortezomib 1.6 mg/m2
Level III(every 21 day cycle):
Day 1: bevacizumab 15 mg/kg, carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.8 mg/m2 Day 8 : bortezomib 1.8 mg/m2; Level II (every 21 day cycle, D8), 1.6 mg/m2; Level III (every 21 day cycle, D8) 1.8 mg/m2; Carboplatin AUC6; Bevacizumab 15 mg/kg; Taxotere 70 + G-CSF
Intervention MeSH terms: Bevacizumab; Carboplatin; Bortezomib; Docetaxel
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lung cancer, Carboplatin, bortezomib, Bevacizumab

Summary:

      A pilot trial of combination of bortezomib, bevacizumab and carboplatin as first line therapy
      in patients with metastatic Non-Small Cell Lung Cancer (NSCLC). Phase I and II study of this
      combination in first line setting will be conducted in order to properly estimate the
      efficacy and safety of this regimen. This will form the basis for future studies comparing
      this combination to what is now considered standard regimen for first line therapy in
      patients with NSCLC, carboplatin, paclitaxel and bevacizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed SCLC (adeno- and large cell, anaplastic carcinoma and
             broncho-alveolar-carcinoma). Patients with squamous-cell histology are eligible with
             extra thoracic or peripheral lung lesions only.

          -  Sputum cytology alone not acceptable evidence of cell type. Cytologic specimens
             obtained by brushing, washings, or needle aspiration of defined lesions will be
             acceptable. Mixed tumors will be categorized by the predominant cell type unless a
             small cell anaplastic elements are present, in which case the patient is ineligible.

          -  Stage III B because of pleural effusion or Stage IV disease

          -  Measurable disease.

          -  Age: 18 years or older

          -  No history of thrombotic, hemorrhagic, or coagulopathy disorders

          -  international normalized ratio (INR<1.5) and a prothrombin time (PTT) no greater than
             normal limits of normal within 1 week prior to registration. NB: subjects with lung
             cancer placed on anticoagulant therapy for a thrombotic event are not eligible for
             this study.

          -  No gross hemoptysis (defined as bright red blood of ½ teaspoon or more)

          -  No central nervous system (CNS) or brain metastasis

          -  Laboratory Criteria (completed <2 weeks before enrollment):

               -  Hematologic: white blood cell (WBC) > 3500/mm3 or absolute neutrophil count (ANC)
                  > 1500/mm3 and platelet count > 100 000/ mm3;

               -  Hepatic: Total bilirubin < 1.5 mg/dl

               -  Renal: Creatinine < 1.5 mg/dl. or calculated

               -  Creatinine clearance > 45 ml/min (NB: Urine protein:creatinine ratio in exclusion
                  criteria)

          -  Eastern Cooperative Oncology Group (ECOG) performance status < 2

          -  Be free of active infection.

          -  Be available for active follow up.

          -  No prior chemotherapy for metastatic disease.

          -  Be disease free for > 5 years if they had a prior second malignancy other than treated
             basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix.

          -  Female subject post-menopausal; surgically sterilized or willing to use an acceptable
             method of birth control for the duration of the study. Male subject agrees to use an
             acceptable method for contraception for the duration of the study.

        Exclusion Criteria:

          -  CNS or brain metastasis

          -  Patient has = or greater Grade 2 peripheral neuropathy within 14 days before
             enrollment.

          -  Known previous sensitivity reactions with boron, or mannitol,

          -  Patients with known HIV positivity

          -  Myocardial infarction within 6 months prior to enrollment or has New York Hospital
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Any ECG abnormality at Screening
             has to be documented by the investigator as not medically relevant.

          -  Blood pressure of >150/100 mmHG

          -  History of myocardial infarction or stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, anticipation of need for major surgical procedure during the course of
             the study.

          -  Minor surgical procedure such as fine needle aspirations or core biopsies within 7
             days prior to day 0

          -  Urine protein: Creatinine ratio > 1.0 at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Lung carcinoma or any histology in close proximity to a major vessel or cavitation

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant. Pregnancy testing is not required for post-menopausal or surgically
             sterilized women.

          -  Patient has received other investigational drugs with 14 days before enrollment or is
             expected to participate in an experiment drug study during this study treatment.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.