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A Phase II Randomized Trial of Fulvestrant and Anastrozole as Consolidation Therapy in Postmenopausal Women With Advanced Non-small Cell Lung Cancer Who Have Received First-line Platinum-based Chemotherapy With or Without Bevacizumab

Phase 2
18 Years
Not Enrolling
Non-small Cell Lung Cancer, Postmenopausal Women

Thank you

Trial Information

A Phase II Randomized Trial of Fulvestrant and Anastrozole as Consolidation Therapy in Postmenopausal Women With Advanced Non-small Cell Lung Cancer Who Have Received First-line Platinum-based Chemotherapy With or Without Bevacizumab

Women invited to participate in this study must be post-menopausal and be 18 years of age or
older. The study is being performed on a total of 100 individuals. Of this group, 75 will
be in the Treatment Groups using Fulvestrant/Anastrozole with our without bevacizumab and 25
will be in the "Best Supportive Care" groups receiving no treatment or just bevacizumab at
the University of Pittsburgh Medical Center.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the progression-free survival.

Outcome Time Frame:

1.5 years

Safety Issue:


Principal Investigator

Ahmad Tarhini, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Institutional Review Board

Study ID:

UPCI 08-131



Start Date:

September 2010

Completion Date:

January 2013

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Postmenopausal Women
  • advanced non-small cell lung cancer
  • postmenopausal
  • bevacizumab
  • fulvestrant
  • anastrozole
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213