Cabazitaxel in Relapsed and Metastatic NSCLC
Cabazitaxel in Relapsed and Metastatic NSCLC
The investigators propose to study the single agent activity of Cabazitaxel in a Phase II
 trial of subjects with relapsed or refractory non-small cell lung cancer pretreated with
 docetaxel, given the fact of its significant activity and its acceptable toxicity profile.
Non small cell lung cancer represents the second most common type of cancer in both men and
 women in the Western world. The availability of new active regimens in the first line setting
 has prompted several investigators to consider second line therapy for patients with advanced
 NSCLC, since a substantial percentage of patients maintain a good PS upon recurrence. On the
 basis of the results of phase III trials docetaxel, erlotinib, gefitinib, or pemetrexed are
 considered as "standard" choices for second-line therapy.

 However, despite the increased availability of different drugs, NSCLC remains a devastating
 disease with median OS which rarely exceeds 12 months.

 Preclinical data of cabazitaxel have demonstrated antitumor activity in models resistant to
 paclitaxel and docetaxel. In cell lines resistant to cytotoxic agents, cabazitaxel induced
 further tumor regression.

 The recommended phase 2 doses for Cabazitaxle were 20 and 25 mg/m2. Cabazitaxel showed
 antitumor activity in solid tumors including docetaxel-refractory metastatic
 castration-resistant prostate cancer and breast cancer.
Inclusion Criteria:

 -  Age>18 years old

 -  Cytologically or histologically documented NSCLC

 -  PS 0-2 (WHO scale)

 -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (at least
 one measurable lesion)

 -  Documented disease progression to previous treatment with docetaxel regimen in 1st or
 2nd line setting assessed by Response Evaluation Criteria in Solid Tumors with at
 least one visceral or soft-tissue metastatic lesion.

 -  Brain metastases are allowed, given that are clinically stable and the patient does
 not present neurologic symptoms.

 -  Previous radiotherapy, either in the adjuvant setting or for the treatment of bone
 metastases, is allowed provided that the measurable lesions are outside the radiation
 fields. Patients who were irradiated to ≥ 40% of bone marrow are not eligible for the
 study.

 -  Patients must have a recent (within 7 days prior to treatment start) biochemical and
 hematogical assessment as defined by adequate bone marrow (absolute neutrophil count
 ≥1.5 x 109 cells/L, platelets ≥100 x 109cells/L and hemoglobin ≥9 g/dL), liver (AST &
 ALT ≤ 2.5x ULN, total bilirubin within normal range) and renal (serum creatinine < 1.5
 x ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated
 according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should
 be excluded) function tests

 -  Absence of any psychological, familial, sociological or geographical condition
 potentially hampering compliance with the study protocol and follow-up schedule.

 -  Before patient enrollment, written informed consent must be given according to ICH/GCP
 and national/local regulations.

 Exclusion Criteria:

 -  Persistence of clinically relevant treatment-related toxicities from previous
 chemotherapy or radiotherapy.

 -  Treatment with other investigational drugs or treatment in another clinical trial
 within the past four weeks before start of treatment or concomitantly with this trial.

 -  Other malignancy within the past five years other than basal cell skin cancer or
 carcinoma in situ of the cervix.

 -  Patient with reproductive potential not implementing accepted and effective method of
 contraception

 -  History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing
 drugs or to docetaxel

 -  Uncontrolled severe illness or medical condition (including uncontrolled diabetes
 mellitus, hypertension, heart failure ≤ NYHA II, history of myocardial infarction
 within the past 6 months, angina, chronic obstructive pulmonary disease (COPD),
 serious infections requiring systemic antibiotic therapy (e.g. antimicrobial,
 antifungal, antiviral)

 -  Concurrent or planned treatment with strong inhibitors or strong inducers of
 cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are
 already on these treatments) (see Appendix A and B)

 -  Prior surgery, radiation, chemotherapy, within 4 weeks prior to treatment

 -  Active grade ≥2 peripheral neuropathy

 -  Active grade ≥2 stomatitis