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Surgery for Early Lung Cancer With Preoperative Erlotinib (Tarceva): A Clinical Phase II Trial

Phase 2
18 Years
95 Years
Open (Enrolling)
Non Small Cell Lung Cancer

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Trial Information

Surgery for Early Lung Cancer With Preoperative Erlotinib (Tarceva): A Clinical Phase II Trial

Treatment will be administered on an outpatient basis. Patients may be identified by
thoracic surgeons, respirologists and/or interventional chest radiologists for study
participation upon clinical and radiographic assessment.

4.2 Diagnostic biopsy, Pretreatment Investigations

If patients have already had a core or FNA biopsy before referral, this material will be
sought from the original pathologist for review and inclusion in the study with appropriate
consent sought. If a patient does not have a biopsy upon presentation to the thoracic
surgeon, and consents to inclusion in the trial, a percutaneous biopsy will be mandated as
part of entry into the study. The order of test will be up to the treating thoracic surgeon.
As part of this procedure a large localizing needle is inserted into the tumour. In
collaboration with pathology, a fine needle is passed through the outer needle and an
immediate diagnosis will be made at the time of fine needle aspiration biopsy. After a
pathologic diagnosis of cancer is confirmed, additional biopsies to obtain material for
correlative studies will be performed through the standard localizing needle, assuming no
complications or technical difficulties have arisen. These studies will be done in
collaboration with thoracic interventional radiologists from Diagnostic Imaging, who perform
the lung fine needle aspirates and biopsies.

All patients will undergo pre-study assessments for symptoms, performance status,
radiographic assessment and blood tests (complete blood count, electrolytes, liver and renal
function tests). Blood samples before treatment and post treatment with erlotinib will be
banked for future serum proteomic analysis. Assessment of response will occur after the
4-week treatment period. Toxicity will be assessed continuously, with patient assessment
weekly on treatment, repeat blood tests at 2 weeks and imaging of measurable disease at 4
weeks. All subjects will be invited to have their initial diagnostic biopsy and subsequent
surgical tumor specimen examined as part of the laboratory correlate component of the study.
Patients will be considered evaluable for pharmacodynamic assessment if they complete at
least 21 of the planned 28 days of therapy.

Patients will have PET-CT scan study done pre- and post-treatment (see section 7). If the
enrolment PET-CT imaging reveals mediastinal disease (IIIA or IIIB) or extensive disease and
this is pathologically confirmed the patient will not be enrolled in the study.

Once the diagnosis is established and assessment completed, oral erlotinib will be
administered at a dose of 150 mg (1 pill) daily for 28 days prior to the planned
mediastinoscopy and/or surgery. Tablets should be taken preferably in the morning with up to
200 mL of water at least 1 hour before or 2 hours after meals. If the patient forgets to
take a dose, they should take the last missed dose as soon as they remember, as long as it
is at least 12 hours before the next dose is due. If patient vomits after taking the dose,
the dose may be retaken if the tablet is seen in the emesis. The last dose of erlotinib will
be administered early in the morning of the mediastinoscopy or surgery.

If the mediastinoscopy reveals the presence of Stage III disease, the patient's
mediastinoscopy samples may still be analyzed as part of the correlative study. Patients
will be followed for 90 days or as long as required after the last dose of erlotinib to
ensure resolution of any erlotinib-related toxicities. However these patients will be
offered standard therapy for stage III disease off study protocol, for example a combination
of chemotherapy, radiation with or without surgical resection. If these patients do proceed
to thoracotomy post-chemotherapy and/or radiotherapy, their resection specimen will not be
eligible for this correlative protocol.

Inclusion Criteria:

- Patients must have cytology or biopsy-proven non-small cell lung carcinoma (NSCLC);

- Preoperative clinical stage must be 1A (T1N0), 1B(T2N0), 2A (T1N1) and 2B (T2N1) by
radiographic criteria;

- Patients must be deemed appropriate candidates for resection by the treating surgeon
and surgical assessment team;

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan;

- Age ³ 18 years;

- ECOG performance status £ 2 (Karnofsky ³ 60%; see Appendix A);

- Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count ³1,500/uL

- platelets ³100,000/uL

- total bilirubin £1.5 times institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) £2 times institutional upper limit of normal

- creatinine £1.5 times institutional upper limit of normal , or creatinine
clearance³50 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal;

- The effects of erlotinib on the developing human fetus are unknown. For this reason,
women of childbearing potential and men must agree to use adequate
contraception (abstinence, hormonal or barrier method of birth control)
prior to study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately;

- Patients on warfarin are not excluded from the trial but are required to have their
INR measured intensively during the initial stages of starting the study drug as
alterations in INR have been noted. This intensive monitoring should entail
measurements (3 X week for the first week then twice weekly for the remainder of the

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients clinically T2N1 (2B), and/or T3N0 (2B) requiring a sleeve lobectomy, and/or
chest wall resection; and tumors with higher staging;

- Patients who have received prior anticancer treatment with chemotherapy, radiotherapy
or EGFR inhibitor therapy;

- Patients who have had a previous diagnosis of cancer within 5 years are excluded
except adequately treated non-melanoma skin cancer, and carcinoma in situ of the
cervix or breast;

- Patients may not be receiving any other investigational or anticancer agents while on

- History of allergic reactions to erlotinib;

- Pre-existing diarrhea ³ NCI CTC Grade 2 (4 to 6 loose stools per day) not controlled
on standard therapy;

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure or evidence of cardiac dysfunction,
unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, poorly
controlled diabetes mellitus, clinically significant or untreated ophthalmologic
(e.g. Sjogrens etc.) or gastrointestinal conditions (e.g. Crohn's disease, ulcerative
colitis) or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study, as the effects of erlotinib on a
developing fetus are unknown. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with
erlotinib, breastfeeding should be discontinued if the mother is treated with this

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with erlotinib.

- Active malignancy at any other site including combined small cell and non-small cell
carcinomas or a pulmonary carcinoid tumor;

- Because drugs that induce CYP3A4 enzymes have been shown to significantly reduce
plasma concentrations of erlotinib, patients with ongoing use of phenytoin,
rifampicin, carbamazepine, barbiturates, rifampicin, or St John's Wort are excluded;

- Incomplete healing from previous surgery;

- Use of any agent that decreases gastric pH, including proton pump inhibitors,
histamine-2 receptor blockers or sodium bicarbonate. Use of calcium or magnesium
based elixirs are not included;

- Concomitant use of CYP3A4 inhibitors, e.g. itraconazole, may result in increased
levels of erlotinib (TARCEVA®). This increase may be clinically relevant since
adverse experiences are related to dose and exposure.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

changes in tumor cell proliferation measured by a 75% reduction of Ki67 Immunohistochemistry (ICH) expression comparing pre and postoperative lung cancer

Outcome Time Frame:

Before surgery and after surgery

Safety Issue:


Principal Investigator

Natasha Leighl, MD FRCPC

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Toronto


Canada: Health Canada

Study ID:

UHN REB#: 06-0052-C



Start Date:

May 2006

Completion Date:

May 2014

Related Keywords:

  • Non Small Cell Lung Cancer
  • Non Small Cell Lung Cancer
  • Lung Cancer
  • Erlotinib
  • Neoadjuvant Treatment
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms