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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Memorial Sloan Kettering Cancer Center
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01967095
First received: October 15, 2013
Last updated: August 12, 2015
Last verified: August 2015
  Purpose

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 Intervention Phase
EGFR-Mutant Lung Cancer
Drug: erlotinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • to determine the maximum tolerated dose (MTD) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    sum of complete responses and partial responses according to RECIST 1.1

  • Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the duration of time from first treatment to time of death.


Estimated Enrollment: 53
Study Start Date: October 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01967095

Contacts
Contact: Helena Yu, MD 646-888-4274
Contact: Gregory Riely, MD, PhD 646-888-4199

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Helena Yu, MD    646-888-4274      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Helena Yu, MD    646-888-4274      
Contact: Gregory Riely, MD, PhD    646-888-4199      
Principal Investigator: Helena Yu, MD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Helena Yu, MD    646-888-4274      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Helena Yu, MD    646-888-4274      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Astellas Pharma US, Inc.
Investigators
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01967095     History of Changes
Other Study ID Numbers: 12-278
Study First Received: October 15, 2013
Last Updated: August 12, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center:
Erlotinib
12-278
CNS involvement

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

ClinicalTrials.gov processed this record on August 27, 2015