Understanding Mechanisms of Acquired Resistance to BIBW2992

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Texas
Boehringer Ingelheim
Information provided by (Responsible Party):
Lecia V. Sequist, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01074177
First received: February 22, 2010
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

In this research study we are looking to see how effective BIBW 2992 is at suppressing the development of the T790M mutation in non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptors (EGFR) are proteins found on the surface of some cancer cells that promote a growth signal. Some cancer drugs for NSCLC work to block this signal from reaching its target on the cancer cells which in turn may slow or stop the cancer from growing. However, many times patients with EGFR mutations will stop responding to these cancer drugs and develop drug-resistance because they have developed a specific EGFR mutation called T790M. BIBW 2992 my prevent the T790M mutation from becoming active and therefore slow disease progression.


Condition Intervention
Non-small Cell Lung Cancer
EGFR Mutations
Drug: BIBW 2992

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Understanding Mechanisms of Acquired Resistance to BIBW2992

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To determine the proportion of patients that have a T790M mutation on their progression biopsy and to compare this with published data for first-generation EGFR tyrosine kinase inhibitors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate the progression-free and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To describe the safety of obtaining repeat tumor biopsies for genotype analysis. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: February 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: BIBW 2992
    Taken orally once a day
Detailed Description:
  • Participants will take tables of BIBW 2992 once a day during each cycle. Each cycle is 28 days (4 weeks).
  • Participants will come to the clinic on Day 1, 8 and 15 of Cycle 1. For Cycle 2 through 8, they woll need to come to the clinic on Day 1. After Cycle 8, they will have study visits every 2 months.
  • The following tests and procedures will be performed at these clinic visits: physical examination, routine blood tests, research blood samples, EKG (every fourth cycle starting cycle 5), ECHO or MUGA (every fourth cycle starting cycle 5), an assessment fo the tumor by CT or MRI scan (every 8 weeks).
  • Participants may continue to participate in this research study as long as their tumor does not grow and their disease does not worsen and they do not have any severe side effects.
  • Participants will have a tumor biopsy performed at the end of their participation in this study if their tumor is growing or if they have a new tumor. The purpose of this biopsy is to assess for the presence or the absence of the mutation T790M.
  Eligibility

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

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed stage IIIB, IV or recurrent non-small cell lung cancer
  • A somatic mutation in epidermal growth factor receptor (EGFR) must be present as documented by a CLIA-certified laboratory
  • There must be radiographic measurable or evaluable disease
  • Participants must be willing, at the time of signing consent, to agree to a future biopsy of their tumor tissue at the time of disease progression, provided such a biopsy is safe and feasible at that time.
  • Performance status must be 0, 1 or 2 on the Eastern Cooperative Oncology Group scale
  • 18 years of age or older
  • Normal organ and marrow function as outlined in the protocol
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

  • Prior EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, or any experimental EGFR TKI agents)
  • Known brain metastases, unless they have undergone definitive therapy and are neurologically stable at the time of study entry
  • Standard chemotherapy or radiation less than 2 weeks of starting BIBW 2992, or experimental systemic cancer therapy less then 4 weeks of starting BIBW 2992. Note that prior palliative radiation to bony disease, CNS disease, or a limited thoracic area is allowed if there is measurable or progressive disease outside the field of radiation.
  • Another malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer)
  • Known pre-existing and clinically active interstitial lung disease
  • Significant gastrointestinal disorders with diarrhea as a major symptom
  • History of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months
  • Cardiac left ventricular function with resting ejection fraction <50%
  • Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
  • Pregnancy or breast feeding
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition of BIBW 2992
  • Life expectancy of < 12 weeks
  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: NCT01074177

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
University of Texas
Boehringer Ingelheim
Investigators
Principal Investigator: Lecia V. Sequist, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Lecia V. Sequist, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01074177     History of Changes
Other Study ID Numbers: 10-092
Study First Received: February 22, 2010
Last Updated: August 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
BIBW 2992
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 18, 2014