Non-small Cell Lung CancerPhase 2NCT00997334
Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC
A Phase 2 study testing Erlotinib in people with Non-small Cell Lung Cancer, run by David M. Jackman, MD at 2 sites in United States.
Trial summary
Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation) in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer research studies and information from those studies suggests that Erlotinib can control the growth of these cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2010to Jan 2017
- Phase
- Phase 2
- 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
- Histologically or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible.
- Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS (the oncogene from the Kirsten rat sarcoma virus) mutations and MET amplification.
- At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria.
- 18 years of age or older
- No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
- 3 or more weeks since prior major surgery
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- 2 or more weeks since prior radiation
- ECOG performance status 0-1
- Life expectancy > 8 weeks
- Adequate hematologic, renal, and hepatic function
- Willingness to undergo repeat tumor biopsy at the time of disease progression.
Who cannot join
- Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment.
- More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
- Prior exposure to erlotinib or other treatments targeting the HER family axis.
- Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- Any process that compromises the ability to swallow and/or absorb oral medication.
- Incomplete healing from previous surgery
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- A history of any of the following autoimmune skin disorders: Sjogren's syndrome, scleroderma, dermatomyositis, and systemic lupus erythematosus.
- Significant medical history or unstable medical conditions.
- Concurrent use of warfarin. Patients must be off warfarin for at least one week prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted.
- Patients who require ongoing concomitant use of one of the strong inhibitors/inducers of CYP3A4.
- Pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations
Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation) in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer research studies and information from those studies suggests that Erlotinib can control the growth of these cancer cells.
Read the detailed description
PRIMARY OBJECTIVE
-To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib (e.g., T790M mutations, MET amplification).
- Correlate these genetic changes with patient demographic data and clinical outcomes (time to progression, survival, sites of recurrence/progression).
- Search for novel mechanisms of acquired resistance to erlotinib.
- Identify whether these genetic changes are present at low levels in initial pretreatment tumor specimens.
SECONDARY OBJECTIVE(S)
- To measure the steady-state plasma concentrations of erlotinib during the course of patients' treatment.
- Determine if the development and/or resolution of skin toxicity is related to plasma erlotinib concentrations.
- Determine if the development of disease progression while on erlotinib is correlated with declines in plasma erlotinib concentrations.
- Assess the plasma levels in patients whose smoking status has been biochemically verified to determine if smoking is associated with lower erlotinib plasma concentration.
- To analyze from both free plasma DNA and DNA from circulating tumor cells of erlotinib-treated patients for the original sensitizing EGFR mutations and genetic changes associated with secondary resistance.
- To measure clinical outcomes in patients with known sensitizing mutations in their tumor EGFR when treated with first-line erlotinib.
- Response rate
- Time to progression
- Median overall survival
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Erlotinib
- Keywords
- erlotinib, EGFR mutation, NSCLC
- 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.
ErlotinibDrug
Also called Tarceva
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib | Experimental | Erlotinib was given at a dose of 150mg orally once per day for 28 days (+/- 3 days); Patients are treated until disease progression or until unaccepted drug toxicity. Receives: Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resistance Mechanism
Participants were classified into 4 potential resistant mechanism groups (4 genetic/ 1 histologic) based on evaluation of rebiopsy tissue: EGFR mutations (T790M mutation, exon 20 insertion), KRAS mutations, MET amplification or small-cell lung cancer (SCLC) transform using established methods.
Measured: Participants were evaluated for incidence of genetic mechanisms of secondary resistance at time of disease progression at which point participants stopped treatment. Progression follow up was up to 3 years in this study cohort.
Secondary outcomes (1)
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Measured: Disease was evaluated radiologically every 8 weeks on treatment (cycle duration=4 weeks). Participants were treated until evidence of disease progression or unacceptable toxicity. Progression follow-up was up to 3 years in this study cohort.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2009 (estimated)
- Study startFeb 2010
- Primary completionMay 2015
- Study completionJan 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- David M. Jackman, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David M. Jackman, MD, Dana-Farber Cancer Institute
- Investigators
- David Jackman, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00997334
- Sponsor's protocol ID
- 09-210
- Other IDs
- NE_OSI4590s
- Status last verified
- Jan 2018
- First submitted
- 16 Oct 2009
- Last updated
- 23 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Redig AJ, Costa DB, Taibi M, Boucher D, Johnson BE, Janne PA, Jackman DM. Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial. JAMA Oncol. 2016 Sep 1;2(9):1240-2. doi: 10.1001/jamaoncol.2016.1304. No abstract available.
PubMed 27387964
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations
- ClinicalTrials.gov ID
- NCT00997334
- Acronym / sponsor ID
- 09-210
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- erlotinib, EGFR mutation, NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- David M. Jackman, MDUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Genentech, Inc.
- Study start
- Feb 2010 (actual)
- Primary completion
- May 2015 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 19 Oct 2009 (estimated)
- Results
- Posted 11 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation) in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer research studies and information from those studies suggests that Erlotinib can control the growth of these cancer cells.
Detailed description
PRIMARY OBJECTIVE
-To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib (e.g., T790M mutations, MET amplification).
- Correlate these genetic changes with patient demographic data and clinical outcomes (time to progression, survival, sites of recurrence/progression).
- Search for novel mechanisms of acquired resistance to erlotinib.
- Identify whether these genetic changes are present at low levels in initial pretreatment tumor specimens.
SECONDARY OBJECTIVE(S)
- To measure the steady-state plasma concentrations of erlotinib during the course of patients' treatment.
- Determine if the development and/or resolution of skin toxicity is related to plasma erlotinib concentrations.
- Determine if the development of disease progression while on erlotinib is correlated with declines in plasma erlotinib concentrations.
- Assess the plasma levels in patients whose smoking status has been biochemically verified to determine if smoking is associated with lower erlotinib plasma concentration.
- To analyze from both free plasma DNA and DNA from circulating tumor cells of erlotinib-treated patients for the original sensitizing EGFR mutations and genetic changes associated with secondary resistance.
- To measure clinical outcomes in patients with known sensitizing mutations in their tumor EGFR when treated with first-line erlotinib.
- Response rate
- Time to progression
- Median overall survival
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib | Experimental | Drug: ErlotinibErlotinib was given at a dose of 150mg orally once per day for 28 days (+/- 3 days); Patients are treated until disease progression or until unaccepted drug toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible.
- Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS (the oncogene from the Kirsten rat sarcoma virus) mutations and MET amplification.
- At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria.
- 18 years of age or older
- No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
Key exclusion criteria (11 listed)
- Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment.
- More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
- Prior exposure to erlotinib or other treatments targeting the HER family axis.
- Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- Any process that compromises the ability to swallow and/or absorb oral medication.
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 |
|---|---|---|
| ErlotinibAlso: Tarceva | Drug | Erlotinib |
Primary outcome
Resistance Mechanism
Time frame: Participants were evaluated for incidence of genetic mechanisms of secondary resistance at time of disease progression at which point participants stopped treatment. Progression follow up was up to 3 years in this study cohort.
Participants were classified into 4 potential resistant mechanism groups (4 genetic/ 1 histologic) based on evaluation of rebiopsy tissue: EGFR mutations (T790M mutation, exon 20 insertion), KRAS mutations, MET amplification or small-cell lung cancer (SCLC) transform using established methods.
1 secondary outcome
Progression-Free Survival
Time frame: Disease was evaluated radiologically every 8 weeks on treatment (cycle duration=4 weeks). Participants were treated until evidence of disease progression or unacceptable toxicity. Progression follow-up was up to 3 years in this study cohort.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27387964Redig AJ, Costa DB, Taibi M, Boucher D, Johnson BE, Janne PA, Jackman DM. Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial. JAMA Oncol. 2016 Sep 1;2(9):1240-2. doi: 10.1001/jamaoncol.2016.1304. No abstract available.
- Individual participant dataSharing planned: No
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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.
David Jackman, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erlotinib in people with Non-small Cell Lung Cancer, run by David M. Jackman, MD 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 11 inclusion and 11 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 23 Feb 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Apr 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?
Resistance Mechanism (time frame: Participants were evaluated for incidence of genetic mechanisms of secondary resistance at time of disease progression at which point participants stopped treatment. Progression follow up was up to 3 years in this study cohort.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00997334, which also lists 1 linked publication.
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 23 Feb 2018.