Fulvestrant and Anastrozole as Consolidation Therapy in Postmenopausal Women With Advanced Non-small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer; Postmenopausal Women
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: fulvestrant (Faslodex); anastrozole (Arimidex); Bevacizumab (Avastin); Best supportive care
Intervention description: Fulvestrant (Faslodex) IM 250 mg monthly after a loading dose of 500 mg on day 1 and 250 mg on day 15 of cycle 1.; Anastrozole (Arimidex) 1 mg orally QD; Bevacizumab (Avastin) 15 mg/kg IV, every 21 days; Subjects will not receive any chemotherapy for NSCLC nor will they received anti-cancer surgery, immunotherapy, radiotherapy or hormonal therapy. Among the therapies they may take are therapies considered acceptable include, but are not limited to, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral
Intervention MeSH terms: Anti-Bacterial Agents; Bevacizumab; Fulvestrant; Anastrozole; Analgesics; Antiemetics
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced non-small cell lung cancer; postmenopausal; bevacizumab; fulvestrant; anastrozole

Summary:

      This research study will test whether dual anti-estrogen therapy (anastrozole and
      fulvestrant) slows the time to when the cancer progresses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC) (no component
             of small cell).

          -  Patients must have stage IIIB (with malignant pleural effusion), stage IV NSCLC (as
             staged by the AJCC Cancer Staging Manual. 6th ed, appendix 1) or stage IV NSCLC as
             staged by the new AJCC staging system

          -  Patients with recurrent NSCLC should have recurred 12 months or more after completion
             of prior chemotherapy given in the context of curative therapy (chemoradiotherapy or
             adjuvant therapy) are eligible

          -  Patients should have been treated with 4 cycles of induction chemotherapy utilizing
             the following regimens: carboplatin/paclitaxel, carboplatin/gemcitabine,
             carboplatin/paclitaxel + bevacizumab, carboplatin/gemcitabine + bevacizumab, or
             carboplatin/pemetrexed +/- bevacizumab, (see Section 3.2 for acceptable doses and
             schedules) and should have CR, PR, or SD as best response.

          -  Patients should not have progressed on prior chemotherapy for metastatic or recurrent
             NSCLC.

          -  Must be postmenopausal female, as defined by the following criteria:

               -  Prior bilateral oophorectomy or

               -  Age greater than 60 years old

               -  Age less than 60 years old and amenorrheic for 12 or more months in the absence
                  of chemotherapy or ovarian suppression with FSH and estradiol in the
                  postmenopausal range.

          -  Registration/randomization should be within 6 weeks of beginning of last cycle of
             chemotherapy

          -  Documented evidence of a tumor response of CR, PR, or SD. Tumor assessment must occur
             between Cycle 4 (Day 1) of induction therapy and the date of randomization. Tumor
             assessment will be per RECIST (Appendix 3) by the treating physician. This response
             does not have to be confirmed in order for the patient to be randomized; however,
             unconfirmed responses will be stratified in the stable disease strata. Positron
             emission tomography (PET) scans and ultrasound may not be used for lesion measurements
             for response determination

          -  ECOG performance status 0, 1 or 2.

          -  At least 18 years of age.

          -  Adequate organ function, including the following:

        Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) greater
        than or equal to 1.0 x10^9/L, platelets greater than or equal to 75 x10^9/L, and hemoglobin
        greater than or equal to 9 g/dL.

        Hepatic: bilirubin less than or equal to 1.5 times the upper limit of normal (ULN),
        alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)
        less than or equal to 2.0 Renal: calculated creatinine clearance (CrCl) ≥45 mL/min based on
        the standard Cockcroft and Gault formula (Cockcroft and Gault 1976).

          -  Prior radiotherapy must be completed at least 3 weeks before study enrollment.
             Patients must have recovered from the acute toxic effects of the treatment prior to
             study enrollment.

          -  Signed informed consent document on file.

          -  Patient compliance and geographic proximity that allow adequate follow up.

          -  Patient must receive on-study therapy no earlier than 21 days and no later than 42
             days from their last cycle (Day 1) of induction therapy.

          -  Patients must have archival tissue samples. Tumor tissue will be submitted for
             assessment of ERa, ERb, PR, VEGF and aromatase expression. The patient must also agree
             to mandatory correlative blood samples at baseline, 5 weeks, 9 weeks, 13 weeks and at
             the time of progression.

          -  Cisplatin may be used instead of carboplatin as part of the initial induction
             chemotherapy regimen, at the discretion of the treating physician investigator. The
             dose and schedule of cisplatin will be according to the standard of care for patients
             with stage IIIB with malignant pleural effusion or stage IV NSCLC as staged by the
             AJCC Cancer Staging Manual, 6th ed, appendix 1, that is equivalent to stage IV NSCLC
             as staged by the new 7th ed AJCC staging system.

        Exclusion Criteria:

          -  Male gender

          -  With the exception of those chemotherapies listed as Inclusion criterion (4) No other
             concomitant biological therapy (e.g. cetuximab) is allowed.

          -  Have received experimental treatment within the last 30 days at the time of study
             entry.

          -  Inability to comply with protocol or study procedures.

          -  A serious concomitant systemic disorder that, in the opinion of the investigator,
             would compromise the patient's ability to complete the study.

          -  Concurrent administration of any other antitumor therapy (except arm B, who are
             allowed to continue with bevacizumab).

          -  Pregnant or breast feeding.

          -  Have a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or
             nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively
             treated at least 5 years previously with no subsequent evidence of recurrence.

          -  Patients with two or more deep vein thromboses, or an active deep vein thrombosis.

          -  Patients taking hormone replacement therapy or other hormonal therapies

          -  The International Normalized Ratio (INR) must be < 1.6 within 28 days prior to
             registration.

          -  Patients with bleeding diathesis (i.e., disseminated intravascular coagulation [DIC],
             clotting factor deficiency) or a history of recent history of hemoptysis (1/2 tsp of
             red blood). Patients on stable long term anticoagulation prior to starting this trial
             are allowed.

          -  History of hypersensitivity to active or inactive excipients of fulvestrant (ie castor
             oil or Mannitol).

          -  Treatment of NSCLC with squamous cell histology with bevacizumab.

          -  No progressive Brain or CNS metastases

          -  No other concurrent anticancer therapy is allowed other than Bevacizumab