Back to resultsLow Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
Primary Purpose
EGFR-Mutant Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
erlotinib
Sponsored by
About this trial
This is an interventional treatment trial for EGFR-Mutant Lung Cancer focused on measuring Erlotinib, 12-278, CNS involvement
Eligibility Criteria
Inclusion Criteria:
- 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%
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Memoral Sloan Kettering Cancer Center
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Rockville Centre
- Memoral Sloan Kettering Cancer Center at Phelps
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
erlotinib
Arm Description
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Response rate (RR)
sum of complete responses and partial responses according to RECIST 1.1
Overall survival (OS)
Overall survival (OS) is defined as the duration of time from first treatment to time of death.
Full Information
NCT ID
NCT01967095
First Posted
October 15, 2013
Last Updated
November 8, 2018
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Astellas Pharma US, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01967095
Brief Title
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
October 15, 2013 (Actual)
Primary Completion Date
November 8, 2018 (Actual)
Study Completion Date
November 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Astellas Pharma US, Inc.
4. Oversight
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
EGFR-Mutant Lung Cancer
Keywords
Erlotinib, 12-278, CNS involvement
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
erlotinib
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
erlotinib
Other Intervention Name(s)
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.
Intervention Description
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.
Primary Outcome Measure Information:
Title
to determine the maximum tolerated dose (MTD)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
to evaluate the safety profile
Description
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.
Time Frame
1 year
Title
Progression Free Survival (PFS)
Description
Progression free survival (PFS) is defined as the duration of time from first treatment to time of progression or death, whichever occurs first.
Time Frame
1 year
Title
Response rate (RR)
Description
sum of complete responses and partial responses according to RECIST 1.1
Time Frame
1 year
Title
Overall survival (OS)
Description
Overall survival (OS) is defined as the duration of time from first treatment to time of death.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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%
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memoral Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Rockville Centre
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memoral Sloan Kettering Cancer Center at Phelps
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
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