ADAM-Afatinib Diarrhea Assessment and Management

NCT01814553 | Completed Phase 3 Results

• 1 other identifier: 1200.167
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 12

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (4)

• 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.

Study Arms (2)

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

Interventions

afatinib DRUG

Daily treatment starting 40 mg per day

Afatinib 40 mg + Loperamide (Cohort 1); Afatinib 40 mg + loperamide prophylactic (Cohort 2)

loperamide DRUG

Follow cohort assignment and diarrhea management guidelines

Afatinib 40 mg + Loperamide (Cohort 1); Afatinib 40 mg + loperamide prophylactic (Cohort 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \. 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.
• \. Patients with meningeal carcinomatosis. 16. Patients with brain or subdural metastases.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (12)

1200.167.01009 Boehringer Ingelheim Investigational Site

Santa Rosa, California, United States

Location

1200.167.01020 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

1200.167.01018 Boehringer Ingelheim Investigational Site

Port Saint Lucie, Florida, United States

Location

1200.167.01012 Boehringer Ingelheim Investigational Site

St. Petersburg, Florida, United States

Location

1200.167.01007 Boehringer Ingelheim Investigational Site

Skokie, Illinois, United States

Location

1200.167.01008 Boehringer Ingelheim Investigational Site

Skokie, Illinois, United States

Location

1200.167.01001 Boehringer Ingelheim Investigational Site

Morristown, New Jersey, United States

Location

1200.167.01014 Boehringer Ingelheim Investigational Site

Corvallis, Oregon, United States

Location

1200.167.01002 Boehringer Ingelheim Investigational Site

Chattanooga, Tennessee, United States

Location

1200.167.01006 Boehringer Ingelheim Investigational Site

Chattanooga, Tennessee, United States

Location

1200.167.01005 Boehringer Ingelheim Investigational Site

Nashville, Tennessee, United States

Location

1200.167.01003 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; Loperamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring

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.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 20, 2013
• Study Start: April 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 31, 2016
• Results First Posted: October 31, 2016

Record last verified: 2016-09

Locations

US (12)