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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01967095
Other study ID # 12-278
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date October 15, 2013
Est. completion date November 8, 2018

Study information

Verified date November 2018
Source Memorial Sloan Kettering Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 53
Est. completion date November 8, 2018
Est. primary completion date November 8, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
United States Memoral Sloan Kettering Cancer Center Basking Ridge New Jersey
United States Memorial Sloan Kettering Commack Commack New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States Memorial Sloan Kettering Rockville Centre Rockville Centre New York
United States Memoral Sloan Kettering Cancer Center at Phelps Sleepy Hollow New York

Sponsors (2)

Lead Sponsor Collaborator
Memorial Sloan Kettering Cancer Center Astellas Pharma US, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 1 year
Secondary 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. 1 year
Secondary 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. 1 year
Secondary Response rate (RR) sum of complete responses and partial responses according to RECIST 1.1 1 year
Secondary Overall survival (OS) Overall survival (OS) is defined as the duration of time from first treatment to time of death. 1 year