Clinical trial NCT00547105: Erlotinib and SBRT in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase II Trial of Erlotinib (Tarceva®) in Combination With Stereotactic Body Radiation Therapy (SBRT) for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
stage IIIA non-small cell lung cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2007-10-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a single arm phase II pilot trial. Patients enrolled on the trial will have been receiving or will begin to receive erlotinib at standard doses (150 mg po per day). SBRT will commence within 4 weeks of the initiation of erlotinib. Maintenance erlotinib will continue until disease progression uncontrollable by SBRT, intolerable toxicity, or death.
Primary purpose: TREATMENT

Brief summary: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Giving erlotinib together with stereotactic body radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving erlotinib together with stereotactic body radiation therapy works in treating patients with locally advanced or metastatic non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* To evaluate the effect of erlotinib and stereotactic body radiotherapy on 6-month progression-free survival of patients with locally advanced or metastatic non-small cell lung cancer.

Secondary

* To describe the actuarial rate of in-field local control and out-of-field disease progression in patients treated with this regimen.
* To evaluate the safety of this regimen in these patients.
* To evaluate overall survival of patients treated with this regimen.
* To evaluate the duration of erlotinib usage and time to initiation of third-line systemic therapy (chemotherapy or biologic agent) in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity. Beginning 1-4 weeks after the initiation of erlotinib hydrochloride, patients undergo stereotactic body radiotherapy.

After completion of study treatment, patients are followed every 3 months.

Eligibility criteria: Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

1. Patients must have biopsy proven NSCLC that is locally advanced or metastatic.
2. Patients must have had failure of at least one prior chemotherapy regimen.
3. Patients must not have started erlotinib therapy more than 4 weeks prior to the initiation of SBRT.
4. Age ≥ 18 years
5. Patients must have measurable disease at baseline.
6. Patients can have up to only 6 discrete active extracranial lesions (≤3 in the liver and ≤3 in the lung) identified by PET scan and also seen on correlative plain film, CT scan, or MRI within 8 weeks prior to the initiation of SBRT.

   1. For patients who have received prior radiotherapy to the primary site in the lung, residual PET activity is difficult to interpret and will not be considered a site of active disease if the CT appearance is stable or improved over an interval of at least three months
   2. Patients who previously received radiotherapy to the primary site will be ineligible if there is CT evidence of disease progression within the past 3 months.
   3. Patients with previously un-irradiated primary sites will be potentially eligible, but special considerations apply (section 4.3.2).
   4. Up to 2 contiguous vertebral metastases will be considered a single site of disease.
7. Patients must have a KPS \>60
8. AST, ALT \& Alkaline phosphates must be ≤ 2.5X the upper limit of normal. Total bilirubin must be within the limit of normal.
9. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm³.
10. Patients should have adequate renal function (serum creatinine ≤1.5 times the ULN).
11. Females of childbearing potential should have a negative pregnancy test.
12. Patients who would be receiving SBRT for lung tumors who are known or suspected by the treating radiation oncologist to have compromised lung function must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1L.
13. Patients must provide verbal and written informed consent to participate in the study.
14. Total bilirubin: within normal institutional limits

Exclusion Criteria Patients who meet any of the following exclusion criteria are not to be enrolled in this study.

1. Patients who previously received radiotherapy to the primary site with CT evidence of disease progression at the primary site within 3 months following the initial radiotherapy.
2. Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
3. Patients with serious, uncontrolled, concurrent infection(s).
4. Significant weight loss (\>10%) in the prior 3 months.
5. Because the tolerance dose of SBRT to the gastrointestinal tract is not established, patients with metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes will not be eligible.
6. Patients with cutaneous metastasis of NSCLC.
7. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers.
8. Patients with more than 6 discrete extra-cranial lesions.
9. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
10. Unwillingness to participate or inability to comply with the protocol for the duration of the study.
11. Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study.
12. Patients who have had prior EGFR inhibitors.

Primary outcomes:
measure: 6 Month Progression-Free Survival
timeFrame: 6 months
Secondary outcomes:
measure: In-field Local Control
timeFrame: 9 months
measure: Number of Participants Without Serious Adverse Events Related to Radiation
timeFrame: 3 years
measure: Overall Survival
timeFrame: up to 5 years
measure: Duration of Erlotinib Use and Time to Initiation of Third-line Systemic Therapy
timeFrame: 3 years
measure: Out-of-field Disease Progression
timeFrame: 9 months
measure: Progression-free Survival
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
Study officials:
affiliation: Simmons Cancer Center
name: Robert D. Timmerman, MD
role: STUDY_CHAIR
References: