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A Phase 1b Study of Intermittent Administration of High Doses of the Irreversible EGFR Inhibitor Afatinib as a Means of Achieving Plasma Levels Active Against Non-small Cell Lung Cancer With Known T790M Mutations


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Carcinoma, Non-Small-Cell Lung

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Trial Information

A Phase 1b Study of Intermittent Administration of High Doses of the Irreversible EGFR Inhibitor Afatinib as a Means of Achieving Plasma Levels Active Against Non-small Cell Lung Cancer With Known T790M Mutations

Inclusion Criteria


Inclusion criteria:

Part A only:

1. Patients with histologically confirmed advanced solid tumours that are metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective. Patients who refuse standard therapy are also eligible.

Part B only:

2. Pathologically confirmed diagnosis of Stage IV (M1a or b) non-small cell lung cancer

3. Documented Epidermal Growth Factor Receptor (EGFR) T790M mutation

4. Progression of disease on a reversible tyrosine kinase inhibitor within 30 days of
starting study drug

Parts A and B:

5. Evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1

6. Age >/= to 18 years

7. Eastern Cooperative Group (ECOG) performance status 0-1

8. Adequate organ function

9. Recovered from any previous therapy-related toxicity to (except for stable sensory neuropathy
10. Written informed consent

11. Ability to take oral medication

Exclusion criteria:

Parts A and B:

1. Chemotherapy, biological therapy, or investigational agents (except erlotinib or
gefitinib) within 4 weeks prior to the start of study treatment

2. Hormonal treatment within 2 weeks prior to the start of study treatment (continued
use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer
is permitted)

3. Radiotherapy within two weeks prior to the start of study treatment (except
palliative radiotherapy given for symptom control)

4. Less than 3 days from prior treatment with gefitinib or erlotinib. Patients with
adverse events related to gefitinib or erlotinib must recover to Grade 1 or less to
be eligible.

5. Major surgery within 4 weeks before starting study treatment or scheduled for surgery
during the projected course of the study

6. Known hypersensitivity to afatinib or the excipients of any of the trial drugs

7. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure New York Heart Association
classification of 3, unstable angina or poorly controlled arrhythmia as determined by
the investigator. Myocardial infarction within 6 months prior to starting study
treatment

8. Women of childbearing potential and men who are able to father a child, unwilling to
be abstinent or use adequate contraception prior to study entry, for the duration of
study participation and for at least 2 months after treatment has ended.

9. Female patients of childbearing potential who are nursing; are pregnant; are not
using an acceptable method of birth control, or do not plan to continue using this
method throughout the study; and do not agree to submit to pregnancy testing required
by this protocol

10. Any history of or concomitant condition that, in the opinion of the investigator,
would compromise the patient's ability to comply with the study or interfere with the
evaluation of the efficacy and safety of the test drug

11. Previous or concomitant malignancies at other sites, except effectively treated
non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ
or effectively treated malignancy that has been in remission for more than 3 years
and is considered to be cured

12. Required treatment with any of the prohibited medications listed in this protocol
that cannot be stopped for the duration of trial participation

13. Known pre-existing Interstitial Lung Disease

14. Any history or presence of poorly controlled gastrointestinal disorders that could
affect the absorption of the study drug (for example, Crohn's disease, ulcerative
colitis, chronic diarrhea, malabsorption) in the opinion of the investigator

15. Active hepatitis B infection (defined as the presence of Hepatitis B DNA), active
hepatitis C infection (defined as the presence of Hepatitis C RNA) and/or known Human
Immunodeficiency Virus carrier

16. Prior participation in a blinded afatinib clinical study, unless permission to
unblind was granted in consultation with the Clinical Monitor of the blinded study

17. Meningeal carcinomatosis

18. Patients with brain or subdural metastases are not eligible, unless they have
completed local therapy and have discontinued use of corticosteroids or have been on
stable doses of corticosteroids for at least 4 weeks before starting study treatment.
Any symptoms attributed to brain metastases must be stable for at least 4 weeks
before starting study treatment

19. QTc interval > 0.47 seconds as measured during screening procedures

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determination of Maximally Tolerated Dose (MTD) of intermittent high-dose afatinib

Outcome Time Frame:

up to 6 months

Safety Issue:

No

Principal Investigator

Boehringer Ingelheim

Investigator Role:

Study Chair

Investigator Affiliation:

Boehringer Ingelheim Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

1200.121

NCT ID:

NCT01647711

Start Date:

July 2012

Completion Date:

December 2013

Related Keywords:

  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

1200.121.01001 Boehringer Ingelheim Investigational SiteAurora, Colorado  
1200.121.01002 Boehringer Ingelheim Investigational SiteBoston, Massachusetts  
1200.121.01004 Boehringer Ingelheim Investigational SiteBoston, Massachusetts  
1200.121.01003 Boehringer Ingelheim Investigational SiteNashville, Tennessee