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CompletedNCT01814553Updated Oct 31, 2016Results posted

ADAM-Afatinib Diarrhea Assessment and Management

A Phase 3 interventional study of afatinib and loperamide in Carcinoma, Non-Small-Cell Lung, sponsored by Boehringer Ingelheim. Completed at 12 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-10-31.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
40
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Carcinoma, Non-Small-Cell Lung
03

In context

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's enrollment of 40 is below the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
  1. 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.
  1. Patients with meningeal carcinomatosis. 16. Patients with brain or subdural metastases.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Afatinib 40 mg + Loperamide (Cohort 1)

    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

  • Experimental
    Afatinib 40 mg + loperamide prophylactic (Cohort 2)

    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

Interventions

  • Drugafatinib

    Daily treatment starting 40 mg per day

  • Drugloperamide

    Follow cohort assignment and diarrhea management guidelines

06

What researchers measure

Primary outcomes

  1. Occurence of CTCAE Grade >= 2 Diarrhea

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

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

Secondary outcomes

  1. Time to Initial Onset of Diarrhea Grade 2 or Higher

    Time to initial onset of diarrhea grade 2 or higher

    Time frame: From first drug administration until end of third treatment course, up to 84 days.

  2. Duration of First Episode of Diarrhea Grade 2 or Higher

    Duration of first episode of diarrhea grade 2 or higher. Please note that the nine patients experienced diarrhea episodes that were not managed according to the protocol specified afatinib treatment interruptions and dose reductions. No patients were excluded from the primary analysis.

    Time frame: From first drug administration until end of third treatment course, up to 84 days.

  3. Changes in Intensity of Diarrhea Over Time

    Percentage of participants with grade 2 or higher diarrhea each week for the first 3 cycles of afatinib treatment

    Time frame: Up to 12 weeks (equivalent to 3 courses)

  4. PFS

    Progression-free survival (PFS). PFS was defined as the time from the start of treatment to an event occurred. In the analyses for the PFS endpoint, an event was defined as disease progression or death, whichever occurred earlier. Data for patients who did not die or progress during the trial were censored at the time of afatinib discontinuation or transition to commercially available afatinib. Median PFS is estimated using Kaplan-Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1).

    Time frame: Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.

07

Results

Posted Oct 31, 2016
Limitations and caveats
In this study, Nine patients experienced diarrhea episodes that were not managed according to the protocol specified afatinib treatment interruptions and dose reductions. No patients were excluded from the primary analysis.

Participant flow

Participant flow — Overall Study
MilestoneAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Started1822
Completed00
Not completed1822
Withdrew: Pd per clinical progression68
Withdrew: Other adverse event45
Withdrew: Withdrawal by subject11
Withdrew: Other than stated78

Outcome measures

PrimaryOccurence of CTCAE Grade >= 2 Diarrhea

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

Time frame:
From first drug administration until 28 days after the end of third treatment course, up to 84 days.
Reported as:
Number · Percentage of participants
Occurence of CTCAE Grade >= 2 Diarrhea
Percentage of participantsAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Occurence of CTCAE Grade >= 2 Diarrhea72.2031.80
SecondaryTime to Initial Onset of Diarrhea Grade 2 or Higher

Time to initial onset of diarrhea grade 2 or higher

Time frame:
From first drug administration until end of third treatment course, up to 84 days.
Reported as:
Mean · days
Time to Initial Onset of Diarrhea Grade 2 or Higher
daysAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Time to Initial Onset of Diarrhea Grade 2 or Higher23.50 ± 22.6415.40 ± 14.97
SecondaryDuration of First Episode of Diarrhea Grade 2 or Higher

Duration of first episode of diarrhea grade 2 or higher. Please note that the nine patients experienced diarrhea episodes that were not managed according to the protocol specified afatinib treatment interruptions and dose reductions. No patients were excluded from the primary analysis.

Time frame:
From first drug administration until end of third treatment course, up to 84 days.
Reported as:
Mean · days
Duration of First Episode of Diarrhea Grade 2 or Higher
daysAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Duration of First Episode of Diarrhea Grade 2 or Higher3.10 ± 4.097.60 ± 5.19
SecondaryChanges in Intensity of Diarrhea Over Time

Percentage of participants with grade 2 or higher diarrhea each week for the first 3 cycles of afatinib treatment

Time frame:
Up to 12 weeks (equivalent to 3 courses)
Reported as:
Number · Percentage of participants
Changes in Intensity of Diarrhea Over Time
Percentage of participantsAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Grade 2: Week 1 (N=2, 1)11.104.50
Grade 2: Week 2 (N=4, 3)22.2013.60
Grade 2: Week 3 (N=3, 3)16.7013.60
Grade 2: Week 4 (N=6, 2)33.309.10
Grade 2: Week 5 (N=2, 0)11.100.00
Grade 2: Week 6 (N=0, 1)0.004.80
Grade 2: Week 7 (N=2, 1)11.805.00
Grade 2: Week 8 (N=3, 0)17.600.00
Grade 2: Week 9 (N=2, 0)11.800.00
Grade 2: Week 10 (N=0, 0)0.000.00
Grade 2: Week 11 (N=2, 0)11.800.00
Grade 2: Week 12 (N=1, 1)5.906.30
Grade >=3: Week 1 (N=1, 1)5.604.50
Grade >=3: Week 2 (N=2, 2)11.109.10
Grade >=3: Week 3 (N=3, 1)16.704.50
Grade >=3: Week 4 (N=0, 1)0.004.50
Grade >=3: Week 5 (N=0, 0)0.000.00
Grade >=3: Week 6 (N=0, 0)0.000.00
Grade >=3: Week 7 (N=1, 0)5.900.00
Grade >=3: Week 8 (N=0, 0)0.000.00
Grade >=3: Week 9 (N=0, 0)0.000.00
Grade >=3: Week 10 (N=1, 0)5.900.00
Grade >=3: Week 11 (N=0, 0)0.000.00
Grade >=3: Week 12 (N=0, 0)0.000.00
SecondaryPFS

Progression-free survival (PFS). PFS was defined as the time from the start of treatment to an event occurred. In the analyses for the PFS endpoint, an event was defined as disease progression or death, whichever occurred earlier. Data for patients who did not die or progress during the trial were censored at the time of afatinib discontinuation or transition to commercially available afatinib. Median PFS is estimated using Kaplan-Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1).

Time frame:
Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
Reported as:
Median · Months
PFS
MonthsAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
PFS15.40 (5.50 to NA)9.90 (5.50 to NA)

Adverse events

Collected over From first drug administration until 28 days after the end of third treatment course, up to 112 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Afatinib 40 mg + Loperamide (Cohort 1)—10/18 (55.6%)18/18 (100%)
Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)—5/22 (22.7%)22/22 (100%)
Most frequent serious events
Showing 10 of 22
Most frequent serious events
EventAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
DiarrhoeaGastrointestinal disorders3/180/22
DehydrationMetabolism and nutrition disorders0/182/22
VomitingGastrointestinal disorders1/180/22
Oedema peripheralGeneral disorders1/180/22
CholecystitisHepatobiliary disorders1/180/22
Abscess limbInfections and infestations1/180/22
CellulitisInfections and infestations1/180/22
Lung infectionInfections and infestations1/180/22
SepsisInfections and infestations1/180/22
HypoglycaemiaMetabolism and nutrition disorders1/180/22
Most frequent other events
Showing 10 of 137
Most frequent other events
EventAfatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
DiarrhoeaGastrointestinal disorders16/1818/22
NauseaGastrointestinal disorders12/188/22
ConstipationGastrointestinal disorders2/1811/22
FatigueGeneral disorders8/185/22
Mucosal inflammationGeneral disorders8/183/22
Dry skinSkin and subcutaneous tissue disorders8/184/22
StomatitisGastrointestinal disorders7/186/22
Decreased appetiteMetabolism and nutrition disorders7/184/22
DehydrationMetabolism and nutrition disorders7/185/22
Dermatitis acneiformSkin and subcutaneous tissue disorders7/188/22

Baseline characteristics

Treated Set : This analysis set includes all entered patients who received at least one dose of investigational treatment (afatinib) and for whom there was documentation that they took at least 1 dose.

Age, Continuous
Age, Continuous(Years)Afatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)Total
Mean69.70 ± 10.8068.00 ± 6.5068.80 ± 8.62
Sex: Female, Male
Sex: Female, Male(Participants)Afatinib 40 mg + Loperamide (Cohort 1)Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)Total
Female121224
Male61016
08

Study locations

12 sites
  • 1200.167.01009 Boehringer Ingelheim Investigational Site
    Santa Rosa, California, 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
  • 1200.167.01012 Boehringer Ingelheim Investigational Site
    St. Petersburg, Florida, United States
  • 1200.167.01007 Boehringer Ingelheim Investigational Site
    Skokie, Illinois, United States
  • 1200.167.01008 Boehringer Ingelheim Investigational Site
    Skokie, Illinois, United States
  • 1200.167.01001 Boehringer Ingelheim Investigational Site
    Morristown, New Jersey, United States
  • 1200.167.01014 Boehringer Ingelheim Investigational Site
    Corvallis, Oregon, United States
  • 1200.167.01002 Boehringer Ingelheim Investigational Site
    Chattanooga, Tennessee, United States
  • 1200.167.01006 Boehringer Ingelheim Investigational Site
    Chattanooga, Tennessee, United States
  • 1200.167.01005 Boehringer Ingelheim Investigational Site
    Nashville, Tennessee, United States
  • 1200.167.01003 Boehringer Ingelheim Investigational Site
    Richmond, Virginia, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 31, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01814553
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Mar 20, 2013
Start date
Apr 2013
Primary completion
Jul 2015
Completion
Jul 2015
Results posted
Oct 31, 2016
Last update
Oct 31, 2016

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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