ADAM-Afatinib Diarrhea Assessment and Management

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)

Sponsors

Lead Sponsor: Boehringer Ingelheim

Source Boehringer Ingelheim
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.

Overall Status Completed
Start Date 2013-04-01
Completion Date 2015-07-01
Primary Completion Date 2015-07-01
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Occurence of CTCAE Grade >= 2 Diarrhea From first drug administration until 28 days after the end of third treatment course, up to 84 days.
Secondary Outcome
Measure Time Frame
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 From first drug administration until end of third treatment course, up to 84 days.
Changes in Intensity of Diarrhea Over Time Up to 12 weeks (equivalent to 3 courses)
PFS Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
Enrollment 40
Condition
Intervention

Intervention Type: Drug

Intervention Name: afatinib

Description: Daily treatment starting 40 mg per day

Intervention Type: Drug

Intervention Name: loperamide

Description: Follow cohort assignment and diarrhea management guidelines

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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Boehringer Ingelheim Study Chair Boehringer Ingelheim
Location
Facility:
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
Location Countries

United States

Verification Date

2016-09-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Afatinib 40 mg + Loperamide (Cohort 1)

Type: Experimental

Description: afatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1.

Label: Afatinib 40 mg + loperamide prophylactic (Cohort 2)

Type: Experimental

Description: afatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1.

Study Design Info

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News