Phase II Study of Combination of Paclitaxel Poliglumex and Alimta for Advanced Non-small Cell Lung Cancer (NSCLC)
Condition: Advanced Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: paclitaxel poliglumex, pemetrexed
Intervention description: The first 6 eligible patients will be enrolled at a dose of 135 mg/m2 paclitaxel poliglumex in combination with 500 mg/m2 of pemetrexed. Patients who experience disease progression without dose-limiting adverse events after the initial cycle will be replaced. Dose escalation to the next dose level can occur provided that no more than 1 of 6 patients experience in initial dose limiting toxicity (IDLT) following 2 cycles of therapy. If ≥ 2 of 6 patients experience IDLTs at the 135 mg/m2 dose, the maximally tolerated dose (MTD) was surpassed and the study will be discontinued
Intervention MeSH terms: Paclitaxel; Pemetrexed; Paclitaxel poliglumex
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: paclitaxel poliglumex; xyotax; alimta; advanced non-small cell lung cancer

Summary:

      This is a non-randomized, single-arm, single-institution, open label, two-stage phase II and
      dose-ranging study designed to evaluate the efficacy and safety of paclitaxel poliglumex in
      combination with pemetrexed in patients with advanced stage IIIB or stage IV NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of locally advanced and/or
             metastatic NSCLC (Stage IIIB or IV).

          -  Bidimensionally measurable lesions or unidimensionally evaluable lesions.

          -  Age ≥ 18 years.

          -  At least one measurable target lesion as defined by Response Evaluation Criteria in
             Solid Tumors (RECIST), which has not been previously treated with local therapy (e.g.
             radiation therapy, chemoembolization, surgery, etc.).

          -  May have received prior chemotherapy (including taxanes) for advanced NSCLC.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  Life expectancy > 12 weeks.

          -  No active infections.

          -  Adequate liver and bone marrow function.

          -  AST<2.5 x ULN, bilirubin <1.5x ULN, alkaline phosphatase<2.5 x ULN (unless bone origin
             and no liver metastases are documented).

          -  ANC ≥ 1,500/uL, platelet count ≥ 100,000/uL.

          -  Normal PT and PTT.

          -  Bisphosphates initiated prior to study entry will be permitted. However, initiation of
             bisphosphonates following study entry is not permitted.

          -  Patients with treated brain metastases must be neurologically stable.

          -  At least 3 weeks since last chemotherapy and recovered from treatment-related adverse
             events ≤ grade 1.

          -  At least 3 weeks since prior radiation and recovered from treatment-related adverse
             events ≤ grade 1.

          -  Women of childbearing potential are eligible for the study, provided they have a
             negative serum or urine pregnancy test within three days of study entry, and an
             adequate method of contraception is used. Acceptable methods of birth control include
             barrier methods (condoms, diaphragms with spermicide) or intrauterine devices (IUD).
             Women whose sole sexual partner is infertile, or who are not sexually active, are also
             eligible.

          -  Able to provide written informed consent.

        Exclusion Criteria:

          -  Grade 2 or greater peripheral neuropathy, according to the National Cancer
             Institute-Common Toxicity Criteria.

          -  Clinically significant pleural, pericardial or abdominal effusions.

          -  Untreated brain metastases.

          -  Patients with previously diagnosed brain metastases will be eligible if they are
             neurologically stable and have recovered from the effects of radiotherapy or surgery
             (≤ grade 2).

          -  Patients with brain metastases must have at least one other site of measurable
             disease.

          -  Concurrent radiotherapy.

          -  Other concurrent cancer treatment-related investigational agent. Investigational
             supportive care medications are permitted.

          -  Concurrent treatment with unfractionated heparin or warfarin.

          -  History of radiotherapy encompassing greater than 50% of the marrow-bearing skeleton.

          -  Prior bone marrow or stem cell transplant.

          -  History of other active malignancy within the last year requiring chemotherapy, not
             including curatively-treated carcinoma in situ of the cervix, or non-melanoma skin
             cancer (basal cell carcinoma or squamous cell carcinoma).

          -  Uncontrolled infection.

          -  Active bleeding, or history of bleeding requiring transfusion within 2 weeks of study
             entry.

          -  Active cardiac disease, as defined as:

          -  Current history of uncontrolled or symptomatic angina.

          -  History of arrhythmias requiring medications or clinically significant arrhythmias,
             with the exception of uncomplicated atrial fibrillation.

          -  Myocardial infarction < 6 months from study entry.

          -  Any other cardiac conditions, which in the opinion of the treating physician, would
             make this protocol unreasonably hazardous for the patient.