Clinical trial NCT01814553: ADAM-Afatinib Diarrhea Assessment and Management
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-03-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Occurence of CTCAE Grade >= 2 Diarrhea
timeFrame: From first drug administration until 28 days after the end of third treatment course, up to 84 days.
Secondary outcomes:
measure: Time to Initial Onset of Diarrhea Grade 2 or Higher
timeFrame: From first drug administration until end of third treatment course, up to 84 days.
measure: Duration of First Episode of Diarrhea Grade 2 or Higher
timeFrame: From first drug administration until end of third treatment course, up to 84 days.
measure: Changes in Intensity of Diarrhea Over Time
timeFrame: Up to 12 weeks (equivalent to 3 courses)
measure: PFS
timeFrame: Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: 1200.167.01009 Boehringer Ingelheim Investigational Site
state: California
city: Orlando
country: United States
facility: 1200.167.01020 Boehringer Ingelheim Investigational Site
state: Florida
city: Port St. Lucie
country: United States
facility: 1200.167.01018 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: 1200.167.01012 Boehringer Ingelheim Investigational Site
state: Florida
city: Skokie
country: United States
facility: 1200.167.01007 Boehringer Ingelheim Investigational Site
state: Illinois
city: Skokie
country: United States
facility: 1200.167.01008 Boehringer Ingelheim Investigational Site
state: Illinois
city: Morristown
country: United States
facility: 1200.167.01001 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Corvallis
country: United States
facility: 1200.167.01014 Boehringer Ingelheim Investigational Site
state: Oregon
city: Chattanooga
country: United States
facility: 1200.167.01002 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: 1200.167.01006 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: 1200.167.01005 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Richmond
country: United States
facility: 1200.167.01003 Boehringer Ingelheim Investigational Site
state: Virginia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: