Clinical trial NCT00237198: Study of Safety and Efficacy of Letrozole Monotherapy as Second-line Endocrine Therapy in Postmenopausal Patients With Advanced Breast Cancer Who Received Previous Anti-estrogen Treatment
Official title: Study of Safety and Efficacy of Letrozole Monotherapy as Second-line Endocrine Therapy in Postmenopausal Patients With Advanced Breast Cancer Who Received Previous Anti-estrogen Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postmenopausal Women With Advanced Breast Cancer
Keywords: Aromatase inhibitor
letrozole
breast cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2005-10-12
Enrollment: 47
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: * Safety and efficacy of letrozole 2.5 mg/day monotherapy as second-line endocrine therapy in postmenopausal patients with advanced breast cancer who received previous anti-estrogen treatment
* To investigate changes in blood drug concentrations and blood hormone kinetics.
* To investigate gene polymorphisms of CYP2A6, an enzyme involved in the metabolism of letrozole


Eligibility criteria: Inclusion Criteria:

* Patients with histologically or cytologically documented breast cancer
* Patients with progressive breast cancer (advanced breast cancer, locoregional recurrence not operative, or metastatic breast cancer)
* Patients with hormone receptor (ER and/or PgR) positive or both unknown.
* Postmenopausal patients between ages 20 and 79 years, inclusive
* Patients with a history of adjuvant therapy or advanced breast cancer treated with anti-estrogens
* Patients with documented measurable or evaluable lesions.
* Patients with sufficient organ function to evaluate the safety
* Patients whose performance status (PS) is 0～2

Exclusion Criteria:

* Patients with diffuse lymphangitis carcinomatosa of the lung or CNS involvement, liver metastasis occupying more than one third of the liver, or inflammatory breast cancer
* Patients with other concurrent or previous malignant disease (excluding contralateral breast cancer, in situ carcinoma of cervix uteri, and adequately treated basal or squamous cell carcinoma of the skin)
* Patients in whom one of the following is the sole manifestation of disease: hilar enlargement, pleural effusion and ascites
* Patients with only blastic bone metastases or a mixed blastic and lytic bone metastases at the same site and no other measurable or evaluable lesions
* Patients with serious current disease such as uncontrolled cardiac diseases and/or uncontrolled diabetes mellitus by any medications (including a historical serious cardiac disease)
* Patients with adrenal insufficiency (treated or untreated) or Cushing's syndrome
* Patients with any of the following previous treatments

  1. Chemotherapy for metastatic and/or locoregional recurrent disease
  2. Previous adjuvant endocrine therapy other than ovariectomy, anti-estrogen treatment, LH-RH analogues or radiation castration
  3. Previous first-line endocrine therapy (e.g., aromatase inhibitors and gastagens) for the treatment of metastatic and/or locoregional recurrent breast cancer other than anti-estrogen or LH-RH analogues treatment
  4. Patients who have not recovered from toxicity caused by previous therapy
  5. For patients on investigational drugs, adequate wash-out periods of at least 7 days in the case of topical investigational drugs and at least 30 days in the case of systemic
  6. Previous bisphosphonate therapy started within 6 months without any other measurable or evaluable lesions
  7. Patients who have not stopped treatment with other anti-estrogen or anti-cancer drugs (other than bisphosphonates) before starting the trial medication

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Safety during treatment
timeFrame: Until disease progression or appearance of unacceptable toxicity whichever comes first
measure: Response Rate during treatment
timeFrame: Until disease progression or appearance of unacceptable toxicity whichever comes first
Secondary outcomes:
measure: Clinical Benefit Rate during treatment
timeFrame: Until disease progression or appearance of unacceptable toxicity whichever comes first
measure: Duration of response
timeFrame: from the first date of response confirmed and the last date of response confirmed
measure: Time to progression
timeFrame: from the first date of response confirmed and the last date of response confirmed
measure: Time to treatment failure
timeFrame: from the date of study initiation and the date of disease progression confirmed or discontinuation other than disease progression
measure: Plasma drug concentration from baseline, every 4 weeks until 28 weeks, at 40 weeks and at 52 weeks
timeFrame: Baseline, 52 weeks
measure: Plasma estrogens level
timeFrame: baseline, 52 weeks
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Matsuyama
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Kooriyama
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Maebashi
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Kure
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kurashiki
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Kitaadachi-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Sunto-gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Cyuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Fukushima
country: Japan
facility: Novartis Investigative Site
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Shizuoka
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: