ADAM-Afatinib Diarrhea Assessment and Management

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase IIIb, Non-randomized, Open-label, Two-cohort Study in Patients With EGFR Mutations-positive Advanced Adenocarcinoma of the Lung, Assessing the Utility of the Afatinib Diarrhea Assessment and Management Guidelines (ADAM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01814553
• Other study ID #: 1200.167
• Status: Completed
• Phase: Phase 3
• First received: March 4, 2013
• Last updated: July 30, 2015
• Start date: April 2013
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a non-randomized, open label, two-cohort, multi-institutional study to evaluate the use of diarrheal management tools intended to facilitate timely intervention and treatment modifications due to afatinib treatment-related diarrhea in patients with EGFR mutations-positive adenocarcinoma of the lung. Patients in Cohort 1 will follow diarrhea management. Patients in Cohort 2 will receive prophylactic loperamide starting the fist day of afatinib treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Pathologically confirmed diagnosis of Stage IIIB or Stage IV adenocarcinoma of the lung, with EGFR mutations-positive status, who are not eligible to receive surgery or chemoradiotherapy. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology, and is a suitable candidate for EGFR-TKI monotherapy, in the opinion of the investigator.

2. Patients must have Epidermal Growth Factor Receptor (EGFR) mutation-positive status according to the institutional standard of care.

3. Patient received no more than one (1) prior chemotherapy for locally advanced or metastatic adenocarcinoma of the lung.

4. Male or female patients Age 18 years and older.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

6. Adequate organ function, defined as all of the following:

• Left Ventricular Ejection Fraction (LVEF) of above 50% or within institution normal values

• Absolute neutrophil count (ANC) above 1500 / mm3.

• Platelet count above 75,000 / mm3.

• Estimated creatinine clearance more than 45ml / min.

• Total Bilirubin less than 1.5 times upper limit of (institutional/central) normal

• Aspartate amino transferase (AST) or alanine amino transferase (ALT) less than three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases less than five times ULN).

7. Recovered from any previous therapy related toxicity to Grade 0 or 1 at study entry

8. Able and willing to follow diarrhea management guidelines provided under this study and to complete Diarrhea Management Worksheet as instructed.

Exclusion criteria:

1. Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment.

2. Prior treatment with EGFR directed small molecules or antibodies.

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

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

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

6. History or presence of clinically relevant cardiovascular abnormalities.

7. 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.

8. Previous or concomitant invasive malignancies at other sites.

9. Known pre-existing interstitial lung disease (ILD).

10. Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug.

14. Active hepatitis B infection, active hepatitis C infection and/or known HIV carrier, who are determined by the investigator as not a suitable candidate to receive EGFR-TKI treatment.

15. Patients with meningeal carcinomatosis. 16. Patients with brain or subdural metastases.

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• afatinib
Daily treatment starting 40 mg per day
• loperamide
Follow cohort assignment and diarrhea management guidelines

Locations

Country	Name	City	State
United States	1200.167.01002 Boehringer Ingelheim Investigational Site	Chattanooga	Tennessee
United States	1200.167.01006 Boehringer Ingelheim Investigational Site	Chattanooga	Tennessee
United States	1200.167.01014 Boehringer Ingelheim Investigational Site	Corvallis	Oregon
United States	1200.167.01001 Boehringer Ingelheim Investigational Site	Morristown	New Jersey
United States	1200.167.01005 Boehringer Ingelheim Investigational Site	Nashville	Tennessee
United States	1200.167.01020 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1200.167.01018 Boehringer Ingelheim Investigational Site	Port St. Lucie	Florida
United States	1200.167.01003 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1200.167.01009 Boehringer Ingelheim Investigational Site	Santa Rosa	California
United States	1200.167.01007 Boehringer Ingelheim Investigational Site	Skokie	Illinois
United States	1200.167.01008 Boehringer Ingelheim Investigational Site	Skokie	Illinois
United States	1200.167.01012 Boehringer Ingelheim Investigational Site	St. Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of CTCAE Grade >= 2 diarrhea		Up to 12 weeks	No
Secondary	Time to initial onset of diarrhea grade 2 or higher		Up to 12 weeks	No
Secondary	Duration of diarrhea grade 2 or higher		Up to 12 weeks	No
Secondary	Changes in intensity of diarrhea over time		Up to 12 weeks	No