Understanding Mechanisms of Acquired Resistance to BIBW2992

• ClinicalTrials.gov Identifier: NCT01074177
• Recruitment Status: Completed
• First Posted: February 24, 2010
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Sponsor: Massachusetts General Hospital
• Collaborators: University of Texas; Boehringer Ingelheim
• Information provided by (Responsible Party): Lecia V. Sequist, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer; EGFR Mutations	Drug: BIBW 2992	Not Applicable

Detailed Description:

• Participants will take tablets 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 will 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 of 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Understanding Mechanisms of Acquired Resistance to BIBW2992
• Study Start Date: February 2011
• Actual Primary Completion Date: March 2017
• Actual Study Completion Date: March 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: BIBW 2992; BIBW 2992 Taken orally once a day	Drug: BIBW 2992; Taken orally once a day; Other Name: Afatinib

Outcome Measures

Primary Outcome Measures :

1. Number of Participants That Have a T790M Mutation on Their Progression Biopsy. [ Time Frame: At the time of disease progression (median duration of 11.4 months from start of treatment) ]

Secondary Outcome Measures :

1. Response Rate [ Time Frame: Baseline and then after the end of every two 28 day cycles until treatment is discontinued; median duration of followup of 19.3 months ]

   The number of participants with either a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

   • CR: Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm
   • PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
2. Median Progression-free and Overall Survival [ Time Frame: start of treatment, at the time of disease progression, time of death ]
   The progression-free and overall survival times. Overall survival is measured from the start of treatment until the time of death or until the participant is lost to follow-up. Progression free survival is measured from the start of treatment until the time of progression, death, or until the participant is lost to follow-up (whichever occurs first). Progression is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression.
3. Number of Participants With Biopsy Complications From Repeat Tumor Biopsies [ Time Frame: 7 days post biopsy and ≥ 30 days post-biopsy ]
   The number of participants with biopsy complications from repeat tumor biopsies taken following disease progression. Biopsy complications are any adverse events considered to be potentially related to the biopsy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

  Study Documents (Full-Text)

Documents provided by Lecia V. Sequist, Massachusetts General Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] October 1, 2013

More Information

• Responsible Party: Lecia V. Sequist, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01074177
• Other Study ID Numbers: 10-092
• First Posted: February 24, 2010
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Last Verified: March 2018

Keywords provided by Lecia V. Sequist, Massachusetts General Hospital:

BIBW 2992; NSCLC

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Afatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action