BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00708214
First received: June 30, 2008
Last updated: December 5, 2013
Last verified: October 2013
  Purpose

Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole


Condition Intervention Phase
Breast Neoplasms
Drug: BIBW 2992
Drug: Letrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of BIBW 2992 Administration in Patients With Hormone Refractory Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Percentage of Progression Free Participants After 16 Weeks of Treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Progression was defined according to 1 of the following criteria: New bone lesion(s) on bone scan or on magnetic resonance imaging; Progression or occurrence of new lesion(s) according to the Response Evaluation Criteria In Solid Tumours version 1.0 (RECIST); an increase in tumour marker CA 15.3 of more than 20 percent,compared with baseline, at 2 consecutive examinations; occurrence of disease-related skeletal events. If a patient did not fulfil any criteria and was withdrawn because of clinical deterioration amounting to PD according to the Investigator, they were considered as having PD.


Secondary Outcome Measures:
  • Number of Participants With Confirmed Objective Response (OR) [ Time Frame: Baseline till progression ] [ Designated as safety issue: No ]
    OR was defined as complete response (CR) or partial response (PR) and was assessed according to RECIST criteria regardless of treatment status.

  • Number of Participants With Clinical Benefit (CB) [ Time Frame: 16 weeks and 24 weeks ] [ Designated as safety issue: No ]
    CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status.

  • Time to RECIST Tumour Reponse [ Time Frame: Baseline till progression ] [ Designated as safety issue: No ]
    The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST criteria.

  • Duration of Confirmed OR [ Time Frame: First occurence or OR till progression or death ] [ Designated as safety issue: No ]
    Duration of confirmed OR is measured from the time of first OR to the time of progression or death (or date of censoring for progression free survival).

  • Progression-free Survival (PFS) [ Time Frame: Baseline till progression, death or data cut-off (04 Jan 2010) ] [ Designated as safety issue: No ]
    PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. Progression was assessed according to RECIST criteria.

  • Overall Survival (OS) [ Time Frame: Baseline till progression, death or data cut-off ] [ Designated as safety issue: No ]
    OS was defined as the time from first treatment to death.

  • Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau at steady state.

  • Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state.

  • Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 57 (Cpre,ss,57) [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
    Cpre,ss,57 represents the pre-dose concentration of afatinib in plasma at steady state on day 57.

  • Pre-dose Concentration of Afatinib in Plasma at Steady Stateon Day 85 (Cpre,ss,85) [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
    Cpre,ss,85 represents the pre-dose concentration of afatinib in plasma at steady state on day 85.

  • Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state

  • Area Under Curve of Letrozole Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    AUC0-tau,ss represents the area under the concentration curve of letrozole in plasma over a uniform dosing interval tau at steady state.

  • Maximum Concentration of Letrozole in Plasma at Steady State (Cmax,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    Cmax,ss represents the maximum measured concentration of letrozole in plasma at steady state.

  • Time From Dosing to the Maximum Concentration of Letrozole in Plasma at Steady State (Tmax,ss) [ Time Frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing ] [ Designated as safety issue: No ]
    tmax,ss represents the time from dosing to the maximum concentration of letrozole in plasma at steady state.

  • Change From Baseline in Ca15.3 [ Time Frame: baseline and day 29 ] [ Designated as safety issue: No ]
    Change from baseline in Ca15.3 tumor marker levels

  • Best Change From Baseline in ECOG Performance Status [ Time Frame: baseline till end of treatment ] [ Designated as safety issue: No ]
    Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead). Improvement is a decrease in ECOG score from baseline of at least 1. Deterioration is an increase in ECOG score from baseline of at least 1


Enrollment: 28
Study Start Date: January 2007
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
To study BIBW 2992 in association with letrozole in hormonoresistant metastatic breast cancer
Drug: BIBW 2992
BIBW 2992 at high and medium dosages
Drug: Letrozole
Letrozole at standard dosage
Letrozole
Hormonotherapy for metastatic breast cancer
Drug: BIBW 2992
BIBW 2992 at high and medium dosages
Drug: Letrozole
Letrozole at standard dosage

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female patients with histologically proven breast adenocarcinoma
  • Presence of metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease, which could include trastuzumab Patients must currently be on letrozole and developed acquired resistance as defined by disease progression on letrozole following previous response (partial response or better, stable disease superior or equal to 24 weeks)

Diagnosis of disease progression inferior or equal to 6 weeks prior to trial entrydefined as:

  1. Increase in the number of bone lesions on bone scan or on MRI AND/OR
  2. Increased pain in an area of known bony metastasis AND superior or equal to 2 serial elevations in CA 15.3 AND/OR
  3. Progression according to RECIST criteria on CT scan, MRI, or x-ray Patients must have documented menopause confirmed by estradiol level inferior to 11 pg/ml

Exclusion criteria:

  • Premenopausal patients
  • Rapidly progressive disease in major organs (i.e. lymphangitic spread in the lung and/or bulky liver metastasis) Patient with brain metastasis Significant cardiovascular diseases Previous treatment with an EGFR and/or HER-2 inhibiting drug(patients who received trastuzumab with chemotherapy but not with letrozole can be enrolled)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708214

Locations
France
1200.5.3306A Boehringer Ingelheim Investigational Site
Caen Cedex, France
1200.5.3304A Boehringer Ingelheim Investigational Site
Nice Cedex 2, France
1200.5.3301A Boehringer Ingelheim Investigational Site
Paris Cedex 10, France
1200.5.3305A Boehringer Ingelheim Investigational Site
Paris Cedex 20, France
1200.5.3302A Boehringer Ingelheim Investigational Site
Saint Cloud, France
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00708214     History of Changes
Other Study ID Numbers: 1200.5, 2006-002814-37
Study First Received: June 30, 2008
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: France: Agence Française de Sécurité Sanitaire des Produits de Santé

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014