Understanding Mechanisms of Acquired Resistance to BIBW2992

NCT01074177 | Completed Results DMC

• 1 other identifier: 10-092
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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 may prevent the T790M mutation from becoming active and therefore slow disease progression.

Conditions

Non-small Cell Lung Cancer; EGFR Mutations

Keywords

BIBW 2992; NSCLC

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Have a T790M Mutation on Their Progression Biopsy.

  At the time of disease progression (median duration of 11.4 months from start of treatment)

Secondary Outcomes (3)

• Response Rate

  Baseline and then after the end of every two 28 day cycles until treatment is discontinued; median duration of followup of 19.3 months

• Median Progression-free and Overall Survival

  start of treatment, at the time of disease progression, time of death

• Number of Participants With Biopsy Complications From Repeat Tumor Biopsies

  7 days post biopsy and ≥ 30 days post-biopsy

Study Arms (1)

BIBW 2992

EXPERIMENTAL

BIBW 2992 Taken orally once a day

Drug: BIBW 2992

Interventions

BIBW 2992 DRUG

Taken orally once a day

Also known as: Afatinib

BIBW 2992

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• University of Texas: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib

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)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Lecia Van Damn Sequist
• Organization: Massachusetts General Hospital

lvsequist@partners.org

617-724-4000

Study Officials

• Lecia V. Sequist, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 22, 2010
• First Posted: February 24, 2010
• Study Start: February 1, 2011
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 9, 2018
• Results First Posted: March 9, 2018

Record last verified: 2018-03

Locations

US (1)