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A Phase II Single-Arm Trial Assessing the Use of an Ex Vivo Sensitivity Assay to Predict Response of Relapsed Metastatic Non-Small Cell Lung Cancer Patients to Erlotinib


Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer

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Trial Information

A Phase II Single-Arm Trial Assessing the Use of an Ex Vivo Sensitivity Assay to Predict Response of Relapsed Metastatic Non-Small Cell Lung Cancer Patients to Erlotinib


OBJECTIVES:

Primary

- Determine whether the extent of inhibition of ERK phosphorylation in lung cancer cells
exposed ex vivo and in vivo to erlotinib hydrochloride significantly differs between
responding and nonresponding patients with relapsed, metastatic or unresectable
non-small cell lung cancer.

Secondary

- Determine whether the extent of inhibition of epidermal growth factor receptor (EGFR)
and AKT phosphorylation in lung cancer cells exposed ex vivo and in vivo to erlotinib
hydrochloride significantly differs between these 2 groups of patients.

- Correlate the extent of inhibition of EGFR, ERK, and AKT phosphorylation in lung cancer
cells exposed ex vivo with erlotinib hydrochloride with in vivo objective tumor
response to erlotinib hydrochloride in these patients.

- Correlate EGFR gene mutation and amplification status with pharmacodynamic evidence of
response to erlotinib hydrochloride in these patients.

OUTLINE: This is an open-label, pilot study.

Patients receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats
every 28 days for at least 2 courses in the absence of disease progression or unacceptable
toxicity.

Patients undergo tumor fine-needle aspiration biopsies under ultrasound or CT scan guidance
at baseline and between days 12-15 for laboratory studies. Laboratory studies include
quantitative western blot and enzyme-linked immunosorbent assays, gene mutation and
amplification, and ex vivo assays. Tumor cells are also analyzed for changes in
phosphorylation status and/or expression levels of pharmacodynamic markers, including total-
and phospho-epidermal growth factor receptor, total- and phospho-ERK, and total- and
phospho-AKT.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed metastatic or unresectable non-small cell
lung cancer

- Relapsed disease

- Failed ≥ 1 prior chemotherapy regimen

- Measurable disease

- Tumor must be accessible to fine-needle aspiration

- No uncontrolled brain metastases

- Patients with brain metastases must have stable neurologic status after local
therapy (surgery or radiotherapy) for ≥ 4 weeks and no neurologic dysfunction
that would preclude evaluation of neurologic and other adverse events

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- WBC > 3,000/mm³

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Bilirubin normal

- PT and activated PTT normal

- Creatinine normal OR creatinine clearance > 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled intercurrent illness, including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would preclude study compliance

- No significant ophthalmologic abnormalities*, including any of the following:

- Severe dry eye syndrome

- Keratoconjunctivitis sicca

- Sjögren's syndrome

- Severe exposure keratopathy

- Disorders that might increase the risk for epithelium-related complications
(e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic
keratitis)

- No serious, nonhealing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 14 days NOTE: *Patients with mild
forms of any of the above ophthalmologic abnormalities, an asymptomatic history, or a
normal ophthalmologic examination allowed at the discretion of the investigator.
Patients with treatable conditions (e.g., infectious keratitis/conjunctivitis or
allergic conjunctivitis) allowed after treatment or resolution of the condition.

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior small molecule inhibitors of epidermal growth factor receptor, including
erlotinib hydrochloride or gefitinib

- At least 4 weeks since prior anticancer therapy, including chemotherapy,
radiotherapy, biologic therapy, or other investigational therapy (6 weeks for
nitrosoureas or mitomycin C)

- More than 14 days since prior major surgery or open biopsy and recovered

- At least 7 days since prior and no concurrent inhibitors of CYP3A4, including any of
the following:

- Itraconazole

- Herbal extracts and tinctures, including any of the following:

- Hydrastis canadensis (goldenseal)

- Uncaria tomentosa (cat's claw)

- Echinacea angustifolia roots

- Trifolium pratense (wild cherry)

- Chamomile

- Licorice root

- Dillapiol

- Naringenin

- No concurrent inducers of CYP3A4, including any of the following:

- Phenytoin

- Carbamazepine

- Rifampin

- Barbiturates

- Hypericum perforatum (St. John's wort)

- No concurrent chemotherapy

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent radiotherapy, including palliative radiotherapy

- No concurrent therapeutic anticoagulation

- No other concurrent anticancer agents or therapies

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Quantitative assessment of phospho-ERK

Principal Investigator

Charles M. Rudin, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

JHOC-J0655, CDR0000512886

NCT ID:

NCT00673569

Start Date:

September 2006

Completion Date:

Related Keywords:

  • Lung Cancer
  • recurrent non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410