Carcinoma, Non-Small-Cell LungPhase 3NCT01814553
ADAM-Afatinib Diarrhea Assessment and Management
A Phase 3 study testing afatinib and loperamide in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- afatinib and loperamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 12 sitesUnited States
- Study dates
- Apr 2013to Jul 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
1200.167.01002 Boehringer Ingelheim Investigational Site
Chattanooga, Tennessee
1200.167.01006 Boehringer Ingelheim Investigational Site
Chattanooga, Tennessee
1200.167.01014 Boehringer Ingelheim Investigational Site
Corvallis, Oregon
1200.167.01001 Boehringer Ingelheim Investigational Site
Morristown, New Jersey
1200.167.01005 Boehringer Ingelheim Investigational Site
Nashville, Tennessee
1200.167.01020 Boehringer Ingelheim Investigational Site
Orlando, Florida
1200.167.01018 Boehringer Ingelheim Investigational Site
Port Saint Lucie, Florida
1200.167.01003 Boehringer Ingelheim Investigational Site
Richmond, Virginia
1200.167.01009 Boehringer Ingelheim Investigational Site
Santa Rosa, California
1200.167.01007 Boehringer Ingelheim Investigational Site
Skokie, Illinois
1200.167.01008 Boehringer Ingelheim Investigational Site
Skokie, Illinois
1200.167.01012 Boehringer Ingelheim Investigational Site
St. Petersburg, Florida
About this study
Official title: 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)
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
- Being tested
- afatinib, loperamide
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afatinibDrug
Daily treatment starting 40 mg per day
loperamideDrug
Follow cohort assignment and diarrhea management guidelines
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: afatinib; Drug: loperamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of CTCAE Grade >= 2 Diarrhea
Overall incidence of patients who experienced diarrhea during the first three courses of afatinib treatment.
Measured: 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
Time to initial onset of diarrhea grade 2 or higher
Measured: From first drug administration until end of third treatment course, up to 84 days.
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.
Measured: From first drug administration until end of third treatment course, up to 84 days.
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
Measured: Up to 12 weeks (equivalent to 3 courses)
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).
Measured: Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2013 (estimated)
- Study startApr 2013
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01814553
- Sponsor's protocol ID
- 1200.167
- Status last verified
- Sep 2016
- First submitted
- 4 Mar 2013
- Last updated
- 31 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01814553
- Acronym / sponsor ID
- 1200.167
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 20 Mar 2013 (estimated)
- Results
- Posted 31 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Afatinib 40 mg + Loperamide (Cohort 1) | Experimental | Drug: afatinib, Drug: loperamideafatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1. |
| Afatinib 40 mg + loperamide prophylactic (Cohort 2) | Experimental | Drug: afatinib, Drug: loperamideafatinib starting 40 mg daily; Cohort 1 will receive loperamide at first sign of diarrhea; Cohort 2 will receive loperamide starting C1D1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| afatinibDaily treatment starting 40 mg per day | Drug | Afatinib 40 mg + Loperamide (Cohort 1), Afatinib 40 mg + loperamide prophylactic (Cohort 2) |
| loperamideFollow cohort assignment and diarrhea management guidelines | Drug | Afatinib 40 mg + Loperamide (Cohort 1), Afatinib 40 mg + loperamide prophylactic (Cohort 2) |
Primary outcome
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.
4 secondary outcomes
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.
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.
Changes in Intensity of Diarrhea Over Time
Time frame: Up to 12 weeks (equivalent to 3 courses)
PFS
Time frame: Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing afatinib and loperamide in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2016.