Fulvestrant and Anastrozole as Consolidation Therapy in Postmenopausal Women With Advanced Non-small Cell Lung Cancer

NCT00932152 | Terminated Phase 2 Results DMC

• 1 other identifier: UPCI 08-131
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-small Cell Lung Cancer; Postmenopausal Women

Keywords

advanced non-small cell lung cancer; postmenopausal; bevacizumab; fulvestrant; anastrozole

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Progression-free Survival.

  1.5 years

Secondary Outcomes (3)

• To Evaluate the Time to Overall Survival, Time to Progression, and Toxicities

  1.5 years

• To Evaluate the Levels of 17b-estradiol, VEGF, E-selectin, Thrombospondin-1 and IGF-1, and Other Biomarkers in the Plasma.

  1.5 years

• To Evaluate Biomarkers (ERa, ERb, PR, VEGF and Aromatase Expression) in Baseline, Archival Tumor Tissue and Correlate Their Expression With Progression-free Survival, Time to Progression, and Overall Survival.

  1.5 years

Study Arms (4)

Arm B, Group 1

ACTIVE COMPARATOR

Best supportive care only: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support PRN

Drug: Best supportive care

Arm B, Group 2

ACTIVE COMPARATOR

Best supportive care and Bevacizumab 15mg/kg every 21 days

Drug: Bevacizumab (Avastin); Drug: Best supportive care

Arm A, Group 1

EXPERIMENTAL

Fulvestrant and anastrozole only

Drug: fulvestrant (Faslodex); Drug: anastrozole (Arimidex)

Arm A, Group 2

EXPERIMENTAL

Fulvestrant, anastrozole and Bevacizumab

Drug: fulvestrant (Faslodex); Drug: anastrozole (Arimidex); Drug: Bevacizumab (Avastin)

Interventions

fulvestrant (Faslodex) DRUG

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.

Arm A, Group 1; Arm A, Group 2

anastrozole (Arimidex) DRUG

Anastrozole (Arimidex) 1 mg orally QD

Arm A, Group 1; Arm A, Group 2

Bevacizumab (Avastin) DRUG

Bevacizumab (Avastin) 15 mg/kg IV, every 21 days

Arm A, Group 2; Arm B, Group 2

Best supportive care DRUG

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

Also known as: Antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support

Arm B, Group 1; Arm B, Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Male gender
• 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

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Fulvestrant; Anastrozole; Bevacizumab; Anti-Bacterial Agents; Analgesics; Antiemetics; Thoracentesis; Pleurodesis; Blood Transfusion; Nutritional Support

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Central Nervous System Agents; Autonomic Agents; Gastrointestinal Agents; Paracentesis; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Drug Therapy; Biological Therapy; Nutrition Therapy

Results Point of Contact

• Title: Ahmad Tarhini, MD
• Organization: University of Pittsburgh

tarhiniaa@upmc.edu

(412) 648-6578

Study Officials

• Ahmad Tarhini, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine and Translational Science

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 3, 2009
• Study Start: September 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: October 19, 2017
• Results First Posted: August 31, 2016

Record last verified: 2017-09

Locations

US (1)