Carcinoma, Non-Small-Cell LungPhase 1NCT01647711
A Study of Intermittent, High-dose Afatinib to Determine the Maximal Tolerated Dose and Assess Activity of This Dose Against Non-small Cell Lung Cancer With T790M Mutations
A Phase 1 study testing Dose escalation followed by treatment with MTD in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 2 sites in United States.
Trial summary
This trial is divided into Part A and Part B. The primary objective of Part A is to establish the Maximal Tolerated Dose of intermittent high dose afatinib. The primary objective of Part B is to assess the response rate of patients with non-small cell lung cancer with EGFR T790M mutations to a dose of intermittent… 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?
- Dose escalation followed by treatment with MTD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2012to Sep 2015
- Phase
- Phase 1
- 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
- Part A only:
- Patients with histologically confirmed advanced solid tumours that are metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients who refuse standard therapy are also eligible.
- Part B only:
- Pathologically confirmed diagnosis of Stage IV (M1a or b) non-small cell lung cancer
- Documented Epidermal Growth Factor Receptor (EGFR) T790M mutation
- Progression of disease on a reversible tyrosine kinase inhibitor within 30 days of starting study drug. Loss of exposure to prior EGFR TKI should not be >30 days; any procedural delay in confirmation of progression is to be discussed with the BI Clinical Monitor.
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- Parts A and B:
- Evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Age >/= to 18 years
- Eastern Cooperative Group (ECOG) performance status 0-1
- Adequate organ function
- Recovered from any previous therapy-related toxicity to </= to Grade 1 at study entry (except for stable sensory neuropathy </= Grade 2 and alopecia)
- Written informed consent
- Ability to take oral medication
Who cannot join
- Parts A and B:
- Chemotherapy, biological therapy, or investigational agents (except erlotinib or gefitinib) within 4 weeks prior to the start of study treatment
- Hormonal treatment within 2 weeks prior to the start of study treatment (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer is permitted)
- Radiotherapy within two weeks prior to the start of study treatment (except palliative radiotherapy given for symptom control)
- Less than 3 days from prior treatment with gefitinib or erlotinib. Patients with adverse events related to gefitinib or erlotinib must recover to Grade 1 or less to be eligible.
- Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
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- Known hypersensitivity to afatinib or the excipients of any of the trial drugs
- History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to starting study treatment
- Women of childbearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended.
- Female patients of childbearing potential who are nursing; are pregnant; are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study; and do not agree to submit to pregnancy testing required by this protocol
- 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 malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured
- Required treatment with any of the prohibited medications listed in this protocol that cannot be stopped for the duration of trial participation
- Known pre-existing Interstitial Lung Disease
- Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (for example, Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption) in the opinion of the investigator
- Active hepatitis B infection (defined as the presence of Hepatitis B DNA), active hepatitis C infection (defined as the presence of Hepatitis C RNA) and/or known Human Immunodeficiency Virus carrier
- Prior participation in a blinded afatinib clinical study, unless permission to unblind was granted in consultation with the Clinical Monitor of the blinded study
- Meningeal carcinomatosis
- Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued use of corticosteroids or have been on stable doses of corticosteroids for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment
- QTc interval > 0.47 seconds as measured during screening procedures
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boehringer Ingelheim Investigational Site
Aurora, Colorado
Boehringer Ingelheim Investigational Site
Boston, Massachusetts
About this study
Official title: A Phase 1b Study of Intermittent Administration of High Doses of the Irreversible EGFR Inhibitor Afatinib as a Means of Achieving Plasma Levels Active Against Non-small Cell Lung Cancer With Known T790M Mutations
This trial is divided into Part A and Part B. The primary objective of Part A is to establish the Maximal Tolerated Dose of intermittent high dose afatinib. The primary objective of Part B is to assess the response rate of patients with non-small cell lung cancer with EGFR T790M mutations to a dose of intermittent afatinib established in Part A.
The secondary objective is to explore tumor response and tumor-derived biological markers of response to afatinib, as well as pharmacokinetic parameters of afatinib.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Dose escalation followed by treatment with MTD
- 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.
Dose escalation followed by treatment with MTDDrug
Fixed 3+3 dose escalation; expansion of MTD cohort
| Study group | Role | What they receive |
|---|---|---|
| Afatinib | Experimental | Establish the Maximal Tolerated Dose of a pulsatile, high-dose regimen of afatinib in patients with advanced solid tumors followed by treatment at that dose or a lower dose in patients with stage IV non-small cell lung cancer harboring EGFR T790M mutations who have progressed on therapy with a reversible tyrosine kinase inhibitor Receives: Drug: Dose escalation followed by treatment with MTD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose Limiting Toxicities
Percentage of participants with Dose Limiting Toxicities (DLTs), based on investigator assessment, for determination of Maximum Tolerated Dose (MTD). MTD was defined as the dose in which less than 2 of up to 6 patients developed a DLT.
Measured: 28 days
Maximum Tolerated Dose
Maximum Tolerated Dose (MTD) was defined as the dose in which less than 2 of up to 6 patients developed a Dose Limiting Toxicity (DLT).
Measured: 28 days
Secondary outcomes (3)
Objective Response Rate for Patients With EGFR T790M Mutations
Objective response rate for patients with Epidermal Growth Factor Receptor (EGFR) T790M mutations. Objective response was defined as Complete Response (CR): Disappearance of all target lesion or Partial Response and (PR): >=30% decrease in the sum of the longest diameter of target lesions, according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
This endpoint was originally planned to be analysed in part B of the study, however as no participants were treated in part B the analysis was performed on the part A participants.
Measured: From first drug administration until last drug administration, up to 420 days
Cmax of Afatinib on Day 3 of Course 1
Maximum measured concentration (Cmax) of afatinib as determined on day 3 of course 1 for patients in Part A
Measured: 47 hours (h) 55 minutes (min), 49h, 50h, 51h, 52h, 53h, 54h, 55h after first dose administration (on day 3 of course 1)
Determination of Dosage for Expansion Cohort in Part B
Determination of dosage for expansion cohort in Part B. Dosage was the MTD or less depending on tolerability.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionSep 2015
- Study completionSep 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 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
- NCT01647711
- Sponsor's protocol ID
- 1200.121
- Status last verified
- Dec 2016
- First submitted
- 16 Jul 2012
- Last updated
- 31 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Intermittent Administration of High Doses of the Irreversible EGFR Inhibitor Afatinib as a Means of Achieving Plasma Levels Active Against Non-small Cell Lung Cancer With Known T790M Mutations
- ClinicalTrials.gov ID
- NCT01647711
- Acronym / sponsor ID
- 1200.121
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 23 Jul 2012 (estimated)
- Results
- Posted 31 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is divided into Part A and Part B. The primary objective of Part A is to establish the Maximal Tolerated Dose of intermittent high dose afatinib. The primary objective of Part B is to assess the response rate of patients with non-small cell lung cancer with EGFR T790M mutations to a dose of intermittent afatinib established in Part A.
The secondary objective is to explore tumor response and tumor-derived biological markers of response to afatinib, as well as pharmacokinetic parameters of afatinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afatinib | Experimental | Drug: Dose escalation followed by treatment with MTDEstablish the Maximal Tolerated Dose of a pulsatile, high-dose regimen of afatinib in patients with advanced solid tumors followed by treatment at that dose or a lower dose in patients with stage IV non-small cell lung cancer harboring EGFR T790M mutations who have progressed on therapy with a reversible tyrosine kinase inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with histologically confirmed advanced solid tumours that are metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients who refuse standard therapy are also eligible.
- Pathologically confirmed diagnosis of Stage IV (M1a or b) non-small cell lung cancer
- Documented Epidermal Growth Factor Receptor (EGFR) T790M mutation
- Progression of disease on a reversible tyrosine kinase inhibitor within 30 days of starting study drug. Loss of exposure to prior EGFR TKI should not be >30 days; any procedural delay in confirmation of progression is to be discussed with the BI Clinical Monitor.
- Evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Key exclusion criteria (20 listed)
- Chemotherapy, biological therapy, or investigational agents (except erlotinib or gefitinib) within 4 weeks prior to the start of study treatment
- Hormonal treatment within 2 weeks prior to the start of study treatment (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer is permitted)
- Radiotherapy within two weeks prior to the start of study treatment (except palliative radiotherapy given for symptom control)
- Less than 3 days from prior treatment with gefitinib or erlotinib. Patients with adverse events related to gefitinib or erlotinib must recover to Grade 1 or less to be eligible.
- Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
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 |
|---|---|---|
| Dose escalation followed by treatment with MTDFixed 3+3 dose escalation; expansion of MTD cohort | Drug | Afatinib |
Primary outcome
Percentage of Participants With Dose Limiting Toxicities
Time frame: 28 days
Percentage of participants with Dose Limiting Toxicities (DLTs), based on investigator assessment, for determination of Maximum Tolerated Dose (MTD). MTD was defined as the dose in which less than 2 of up to 6 patients developed a DLT.
Maximum Tolerated Dose
Time frame: 28 days
Maximum Tolerated Dose (MTD) was defined as the dose in which less than 2 of up to 6 patients developed a Dose Limiting Toxicity (DLT).
3 secondary outcomes
Objective Response Rate for Patients With EGFR T790M Mutations
Time frame: From first drug administration until last drug administration, up to 420 days
Cmax of Afatinib on Day 3 of Course 1
Time frame: 47 hours (h) 55 minutes (min), 49h, 50h, 51h, 52h, 53h, 54h, 55h after first dose administration (on day 3 of course 1)
Determination of Dosage for Expansion Cohort in Part B
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dose escalation followed by treatment with MTD in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 2 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 20 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 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Jan 2017). 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?
Percentage of Participants With Dose Limiting Toxicities (time frame: 28 days). The study lists 2 primary outcomes in all. 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 Jan 2017.