ADAM-Afatinib Diarrhea Assessment and Management | NCT01814553

NCT01814553

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Afatinib 40 mg + Loperamide (Cohort 1)	Experimental	afatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1.	Drug: afatinib Drug: loperamide
Afatinib 40 mg + loperamide prophylactic (Cohort 2)	Experimental	afatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1.	Drug: afatinib Drug: loperamide

Name	Type	Description	Arm Group Labels	Other Names
afatinib	Drug	Daily treatment starting 40 mg per day	Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + loperamide prophylactic (Cohort 2)

Measure	Description	Time Frame
Occurence of CTCAE Grade >= 2 Diarrhea	Overall incidence of patients who experienced diarrhea during the first three courses of afatinib treatment.	From first drug administration until 28 days after the end of third treatment course, up to 84 days.

Measure	Description	Time Frame
Time to Initial Onset of Diarrhea Grade 2 or Higher	Time to initial onset of diarrhea grade 2 or higher	From first drug administration until end of third treatment course, up to 84 days.
Duration of First Episode of Diarrhea Grade 2 or Higher

Eligibility Module

Eligibility Criteria

Inclusion criteria:

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.
Patients must have Epidermal Growth Factor Receptor (EGFR) mutation-positive status according to the institutional standard of care.
Patient received no more than one (1) prior chemotherapy for locally advanced or metastatic adenocarcinoma of the lung.
Male or female patients Age 18 years and older.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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).
Recovered from any previous therapy related toxicity to Grade 0 or 1 at study entry
Able and willing to follow diarrhea management guidelines provided under this study and to complete Diarrhea Management Worksheet as instructed.

Exclusion criteria:

Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment.
Prior treatment with EGFR directed small molecules or antibodies.
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).
Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
Known hypersensitivity to afatinib or the excipients of any of the trial drugs.
History or presence of clinically relevant cardiovascular abnormalities.
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.
Previous or concomitant invasive malignancies at other sites.
Known pre-existing interstitial lung disease (ILD).
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.

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1200.167.01009 Boehringer Ingelheim Investigational Site		Santa Rosa	California		United States
1200.167.01020 Boehringer Ingelheim Investigational Site

Arm/Group Information

ID	Title	Description
FG000	Afatinib 40 mg + Loperamide (Cohort 1)	Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
FG001	Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)	Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Afatinib 40 mg + Loperamide (Cohort 1)	Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Occurence of CTCAE Grade >= 2 Diarrhea

Overall incidence of patients who experienced diarrhea during the first three courses of afatinib treatment.

Treated set

Posted

Number

Percentage of participants

From first drug administration until 28 days after the end of third treatment course, up to 84 days.

ID	Title	Description
OG000	Afatinib 40 mg + Loperamide (Cohort 1)	Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Afatinib 40 mg + Loperamide (Cohort 1)	Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms

ID	Term
D000577	Amides
D009930	Organic Chemicals
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring