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Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer

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ClinicalTrials.gov Identifier: NCT01967095
Recruitment Status : Completed
First Posted : October 22, 2013
Last Update Posted : November 12, 2018
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE October 15, 2013
First Posted Date  ICMJE October 22, 2013
Last Update Posted Date November 12, 2018
Actual Study Start Date  ICMJE October 15, 2013
Actual Primary Completion Date November 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01967095 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2013)
  • to evaluate the safety profile [ Time Frame: 1 year ]
    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) [ Time Frame: 1 year ]
    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) [ Time Frame: 1 year ]
    sum of complete responses and partial responses according to RECIST 1.1
  • Overall survival (OS) [ Time Frame: 1 year ]
    Overall survival (OS) is defined as the duration of time from first treatment to time of death.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
Official Title  ICMJE A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE EGFR-Mutant Lung Cancer
Intervention  ICMJE Drug: erlotinib
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.
Other Names:
  • 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.
Study Arms  ICMJE Experimental: erlotinib

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: Drug: erlotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 7, 2015)
53
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2013)
58
Actual Study Completion Date  ICMJE November 8, 2018
Actual Primary Completion Date November 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01967095
Other Study ID Numbers  ICMJE 12-278
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Astellas Pharma US, Inc.
Investigators  ICMJE
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP