Phase II Study of Cabazitaxel-XRP6258 in Advanced Non-Small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer (NSCLC); Stage IV NSCLC; Metastatic NSCLC
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cabazitaxel-XRP6258 (3-week cycle); Cabazitaxel-XRP6258 (5-week cycle)
Intervention description: Subjects in Schedule A will begin with an initial dose of 20 mg/m2 every 3 weeks as a 1 hour IV infusion. If no dose limiting toxicities are experienced after cycle 1, then the dose will be escalated to 25 mg/m2. Treatment with Cabazitaxel-XRP6258 will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity or withdrawal of consent. Further treatment after 6 cycles of treatment in patients who achieved an objective response or stable disease, and no significant toxicity will be an individual decision from the investigator.; Subjects in Schedule B will begin with an initial dose of 8.4 mg/m2 as a 1 hour IV infusion on days 1, 8, 15, and 22 of a 5-week cycle. If no dose limiting toxicities are experienced after cycle 1, then the dose will be escalated to 10 mg/m2. Treatment with Cabazitaxel-XRP6258 will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity or withdrawal of consent. Further treatment after 6 cycles of treatment in patients who achieved an objective response or stable disease, and no significant toxicity will be an individual decision from the investigator.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: Non-small cell lung cancer; Cabazitaxel-XRP6258; P-glycoprotein; taxane; Advanced NSCLC

Summary:

      Lung cancer is the leading cause of cancer death worldwide and in the United States. The
      majority of lung cancers are non-small cell lung cancer (NSCLC). The majority of NSCLC cases
      are advanced at the time of diagnosis. Chemotherapy has improved overall survival but remains
      limited at < 12 months median overall survival. New approaches are needed for second line
      chemotherapy treatment. Cabazitaxel-XRP6258 has shown increased overall survival in
      metastatic prostate cancer and it is hopeful it can do the same in advanced NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not
             specified)

          -  Subjects who have failed first line chemotherapy (platinum doublets or non- platinum
             doublets [previous taxane exposure is allowed]) for Stage IV NSCLC.

          -  Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors
             (RECIST)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Age > 18 years old

          -  Adequate bone marrow, liver and renal function, defined as:

               -  Absolute neutrophil count (ANC) greater than or equal to 1500/ul

               -  Hemoglobin greater than or equal to 10 g/dl

               -  Platelet count greater than or equal to 100,000/ul

               -  Total bilirubin less than or equal to 1.5 x upper limit of normal (except in
                  subjects with documented Gilbert's syndrome)

               -  AST/ALT less than or equal to 1.5 x upper limit of normal

               -  Serum creatinine less than or equal to 1.8 mg/dl

          -  Fully recovered from any previous surgery (at least 4 weeks since major surgery)

          -  Fully recovered from previous radiation therapy (at least 2 weeks)

          -  All subjects must agree to practice approved methods of birth control (if applicable).
             A negative pregnancy test must be documented during the screening period for women of
             childbearing potential.

          -  Written informed consent and authorization to use and disclose health information
             (HIPAA) must be signed by the subject.

          -  Subjects with symptomatic brain metastases should be adequately treated and controlled
             prior to the initiation of the study. Subjects with asymptomatic brain metastases will
             be allowed in the study without any prior therapy for brain metastases.

        Exclusion Criteria:

          -  Concurrent cancer chemotherapy, biologic therapy or radiotherapy

          -  Administration of any investigational agent within 28 days prior to administration of
             current therapy

          -  Untreated symptomatic brain metastases

          -  Greater than or equal to Grade 2 neuropathy

          -  Concurrent serious infection

          -  Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor,
             which is likely to compromise subject safety and affect the outcome of the study.

          -  Treatment for a cancer other the NSCLC within 5 years prior to enrollment, with the
             exception of basal cell carcinoma or carcinoma in situ of the cervix

          -  Any evidence of history of hypersensitivity for the taxane class of chemotherapy drugs

          -  History of positive serology for HIV

          -  Psychiatric disorder that prevents subjects from providing informed consent or
             following protocol instructions

          -  Pregnant or lactating women