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 July 2014 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: July 22, 2014
Last verified: July 2014

October 15, 2013
July 22, 2014
October 2013
October 2015   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01967095 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
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.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
EGFR-Mutant Lung Cancer
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.
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.
Intervention: Drug: erlotinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
70
October 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • MSKCC pathologically-proven diagnosis of EGFR-Mutant locally advanced Stage III not amenable to definitive, curative treatment or Stage IV or recurrent non-small cell lung cancer
  • 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.

Exclusion Criteria:

  • 1. 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 (previously treated or untreated) are eligible.
  • Women who are breastfeeding or pregnant.
  • Any evidence of clinically active interstitial lung disease.
Both
18 Years and older
No
Contact: Helena Yu, MD 646-888-4274
Contact: Gregory Riely, MD, PhD 646-888-4199
United States
 
NCT01967095
12-278
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Astellas Pharma US, Inc.
Principal Investigator: Helena Yu, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
July 2014

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