EGFR-Mutant Lung CancerPhase 1NCT01967095
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
A Phase 1 study testing erlotinib in people with EGFR-Mutant Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
The purpose of this study is to test the safety of different ways of taking erlotinib. The investigators want to find out what effects, good and/or bad, combination daily low dose and twice weekly high dose erlotinib has on the patient and lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR-Mutant 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
- 53 participants
- Where
- 5 sitesUnited States
- Study dates
- 15 Oct 2013to 8 Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- MSKCC pathologically-proven diagnosis locally advanced Stage III not amenable to definitive, curative treatment or Stage IV or recurrent non-small cell lung cancer
- Documented presence of EGFR mutation confirmed by MSKCC or a local facility.
- No prior treatment with erlotinib, gefitinib, or other EGFR tyrosine kinase inhibitors
- Age ≥ 18 years
- Measurable (RECIST 1.1) indicator lesion not previously irradiated.
- Karnofsky Performance Status ≥ 70%
Show all 11Show fewer
- Ability to take oral medications
- A negative serum pregnancy test obtained within 4 weeks prior to the start of treatment in all women of child-bearing potential.
- All women of child bearing potential and sexually active men must agree to use adequate methods of birth control throughout the study which includes use of oral contraceptives with an additional barrier methods, double barrier methods, Depo-Provera, permanent sterilization of patient or partner or total abstinence.
- Expansion A:
- brain metastases or leptomeningeal not previously treated with radiation or surgery
Who cannot join
- Inadequate recovery from any toxicity related to prior treatment (to Grade 2 or baseline).
- Inadequate hematologic function defined as ANC < 1000 cells/mm³, Platelet count <75,000/mm³ or Hemoglobin <9.0g/dL.
- Inadequate hepatic function defined by AST/ALT >3x upper limit of normal (ULN), Total bilirubin>2x ULN, Alkaline phosphatase >3x ULN.
- Symptomatic brain metastasis requiring radiation therapy or escalating doses of steroids.
- Patients with clinically stable brain metastases or leptomeningeal disease (previously treated or untreated) are eligible. Patients in expansion cohort A must have at least one untreated CNS lesion
- Women who are breastfeeding or pregnant.
- Any evidence of clinically active interstitial lung disease.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York, 11570
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, 10591
About this study
Official title: A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
The purpose of this study is to test the safety of different ways of taking erlotinib. The investigators want to find out what effects, good and/or bad, combination daily low dose and twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are also seeing whether different schedules of erlotinib are better at treating lung cancer that has spread to the central nervous system.
CNS expansion phase:
The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the expansion cohorts will undergo the same treatment plan as the patients in the dose expansion cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish the first 28 day (cycle 1) treatment period.
- Conditions
- EGFR-Mutant Lung Cancer
- Being tested
- erlotinib
- Keywords
- Erlotinib, 12-278, CNS involvement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinibDrug
Also called The assigned dosing schedule will be repeated weekly x 3 to complete a 3 week, (21 day) cycle. Cycle 1 will be 4 weeks to account for one week of lead in, pulse dose erlotinib only.
Cycle 1, week 1 (D1-D7) will consist of pulse dose erlotinib on D1 \& D2 without daily low dose erlotinib on D3-7. For all subsequent weeks, patients will take high dose erlotinib on D1 \& D2, \& will receive erlotinib 50 mg oral daily x 5 days on days 3-7. On days 1 \& 2, patients will take one of the following doses of erlotinib, depending on the dose cohort they are enrolled in: Dose level 1 600 mg oral daily on D1, D2 Dose level 2 750 mg oral daily on D1, D2 Dose level 3 900 mg oral daily on D1, D2 Dose level 4 1050 mg oral daily on D1, D2. An additional Dose -1 (pulse dose erlotinib on D1, D2 with 25 mg oral daily x 5 days in D3-D7) will be reserved, in the unlikely situation that Dose 1 is proved too toxic. If Dose -1 is tolerated well (600mg oral daily D1, D2 \& 25mg oral daily D3-D7), pulse dose escalation can continue as described above, with erlotinib at the daily low dose of 25 mg oral on D3-D7.
| Study group | Role | What they receive |
|---|---|---|
| erlotinib | Experimental | This protocol is a phase 1, single arm, open label study of combination daily low dose erlotinib plus twice weekly high dose erlotinib in patients with EGFR-Mutant lung cancer who have not yet received erlotinib or gefitinib. Six dose levels are planned for escalation, with the pulse dose erlotinib increasing.
Expansion cohort A: Treat an additional 19 pts at the MTD with CNS involvement at diagnosis Receives: Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
to determine the maximum tolerated dose (MTD)
The study will use a standard 3+3 dose escalation design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
Measured: 1 year
Secondary outcomes (4)
to evaluate the safety profile
Toxicity will be graded according to NCI CTCAE, version 4.0. The analysis of safety/tolerability data will be descriptive; toxicity events will be individually tabulated.
Measured: 1 year
Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the duration of time from first treatment to time of progression or death, whichever occurs first.
Measured: 1 year
Response rate (RR)
sum of complete responses and partial responses according to RECIST 1.1
Measured: 1 year
Overall survival (OS)
Overall survival (OS) is defined as the duration of time from first treatment to time of death.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2013 (estimated)
- Study start15 Oct 2013
- Primary completion8 Nov 2018
- Study completion8 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFR-Mutant Lung CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Responsible party
- Sponsor
- Investigators
- Helena Yu, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01967095
- Sponsor's protocol ID
- 12-278
- Status last verified
- Nov 2018
- First submitted
- 15 Oct 2013
- Last updated
- 13 Nov 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
- ClinicalTrials.gov ID
- NCT01967095
- Acronym / sponsor ID
- 12-278
- Conditions
- EGFR-Mutant Lung Cancer
- Keywords
- Erlotinib, 12-278, CNS involvement
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Study start
- 15 Oct 2013 (actual)
- Primary completion
- 8 Nov 2018 (actual)
- Study completion
- 8 Nov 2018 (actual)
- First posted
- 22 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety of different ways of taking erlotinib. The investigators want to find out what effects, good and/or bad, combination daily low dose and twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are also seeing whether different schedules of erlotinib are better at treating lung cancer that has spread to the central nervous system.
CNS expansion phase:
The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the expansion cohorts will undergo the same treatment plan as the patients in the dose expansion cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish the first 28 day (cycle 1) treatment period.
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: erlotinibThis protocol is a phase 1, single arm, open label study of combination daily low dose erlotinib plus twice weekly high dose erlotinib in patients with EGFR-Mutant lung cancer who have not yet received erlotinib or gefitinib. Six dose levels are planned for escalation, with the pulse dose erlotinib increasing. Expansion cohort A: Treat an additional 19 pts at the MTD with CNS involvement at diagnosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- MSKCC pathologically-proven diagnosis locally advanced Stage III not amenable to definitive, curative treatment or Stage IV or recurrent non-small cell lung cancer
- Documented presence of EGFR mutation confirmed by MSKCC or a local facility.
- No prior treatment with erlotinib, gefitinib, or other EGFR tyrosine kinase inhibitors
- Age ≥ 18 years
- Measurable (RECIST 1.1) indicator lesion not previously irradiated.
Key exclusion criteria (7 listed)
- Inadequate recovery from any toxicity related to prior treatment (to Grade 2 or baseline).
- Inadequate hematologic function defined as ANC < 1000 cells/mm³, Platelet count <75,000/mm³ or Hemoglobin <9.0g/dL.
- Inadequate hepatic function defined by AST/ALT >3x upper limit of normal (ULN), Total bilirubin>2x ULN, Alkaline phosphatase >3x ULN.
- Symptomatic brain metastasis requiring radiation therapy or escalating doses of steroids.
- Patients with clinically stable brain metastases or leptomeningeal disease (previously treated or untreated) are eligible. Patients in expansion cohort A must have at least one untreated CNS lesion
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: The assigned dosing schedule will be repeated weekly x 3 to complete a 3 week, (21 day) cycle. Cycle 1 will be 4 weeks to account for one week of lead in, pulse dose erlotinib only.Cycle 1, week 1 (D1-D7) will consist of pulse dose erlotinib on D1 \& D2 without daily low dose erlotinib on D3-7. For all subsequent weeks, patients will take high dose erlotinib on D1 \& D2, \& will receive erlotinib 50 mg oral daily x 5 days on days 3-7. On days 1 \& 2, patients will take one of the following doses of erlotinib, depending on the dose cohort they are enrolled in: Dose level 1 600 mg oral daily on D1, D2 Dose level 2 750 mg oral daily on D1, D2 Dose level 3 900 mg oral daily on D1, D2 Dose level 4 1050 mg oral daily on D1, D2. An additional Dose -1 (pulse dose erlotinib on D1, D2 with 25 mg oral daily x 5 days in D3-D7) will be reserved, in the unlikely situation that Dose 1 is proved too toxic. If Dose -1 is tolerated well (600mg oral daily D1, D2 \& 25mg oral daily D3-D7), pulse dose escalation can continue as described above, with erlotinib at the daily low dose of 25 mg oral on D3-D7. | Drug | erlotinib |
Primary outcome
to determine the maximum tolerated dose (MTD)
Time frame: 1 year
The study will use a standard 3+3 dose escalation design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
4 secondary outcomes
to evaluate the safety profile
Time frame: 1 year
Progression Free Survival (PFS)
Time frame: 1 year
Response rate (RR)
Time frame: 1 year
Overall survival (OS)
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2018.
- Memorial Sloan Kettering Cancer CenterLink 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.
Helena Yu, MD principal investigator
Memorial Sloan Kettering Cancer Center
5 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 erlotinib in people with EGFR-Mutant Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 5 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 7 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 13 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
to determine the maximum tolerated dose (MTD) (time frame: 1 year). 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 13 Nov 2018.