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ADAM-Afatinib Diarrhea Assessment and Management

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ClinicalTrials.gov Identifier: NCT01814553
Recruitment Status : Completed
First Posted : March 20, 2013
Results First Posted : October 31, 2016
Last Update Posted : October 31, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE March 4, 2013
First Posted Date  ICMJE March 20, 2013
Results First Submitted Date  ICMJE July 1, 2016
Results First Posted Date  ICMJE October 31, 2016
Last Update Posted Date October 31, 2016
Study Start Date  ICMJE April 2013
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
Occurence of CTCAE Grade >= 2 Diarrhea [ Time Frame: From first drug administration until 28 days after the end of third treatment course, up to 84 days. ]
Overall incidence of patients who experienced diarrhea during the first three courses of afatinib treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2013)
Occurence of CTCAE Grade >= 2 Diarrhea [ Time Frame: Up to 12 weeks ]
Change History Complete list of historical versions of study NCT01814553 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
  • 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. ]
    Time to initial onset of diarrhea grade 2 or higher
  • Duration of First Episode of Diarrhea Grade 2 or Higher [ Time Frame: From first drug administration until end of third treatment course, up to 84 days. ]
    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.
  • Changes in Intensity of Diarrhea Over Time [ Time Frame: Up to 12 weeks (equivalent to 3 courses) ]
    Percentage of participants with grade 2 or higher diarrhea each week for the first 3 cycles of afatinib treatment
  • PFS [ Time Frame: Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment. ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2013)
  • Time to Initial Onset of Diarrhea Grade 2 or Higher [ Time Frame: Up to 12 weeks ]
  • Duration of diarrhea grade 2 or higher [ Time Frame: Up to 12 weeks ]
  • Changes in Intensity of Diarrhea Over Time [ Time Frame: Up to 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ADAM-Afatinib Diarrhea Assessment and Management
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: afatinib
    Daily treatment starting 40 mg per day
  • Drug: loperamide
    Follow cohort assignment and diarrhea management guidelines
Study Arms  ICMJE
  • 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.
    Interventions:
    • 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.
    Interventions:
    • Drug: afatinib
    • Drug: loperamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 5, 2014)
40
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2013)
80
Actual Study Completion Date  ICMJE July 2015
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01814553
Other Study ID Numbers  ICMJE 1200.167
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP