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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 : Active, not recruiting
First Posted : October 22, 2013
Last Update Posted : May 10, 2017
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
EGFR-Mutant Lung Cancer Drug: erlotinib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 15, 2013
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
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

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Response rate (RR) [ Time Frame: 1 year ]
    sum of complete responses and partial responses according to RECIST 1.1

  4. Overall survival (OS) [ Time Frame: 1 year ]
    Overall survival (OS) is defined as the duration of time from first treatment to time of death.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01967095

United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York, United States, 11570
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Astellas Pharma US, Inc.
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01967095     History of Changes
Other Study ID Numbers: 12-278
First Posted: October 22, 2013    Key Record Dates
Last Update Posted: May 10, 2017
Last Verified: May 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:
CNS involvement

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action