Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer
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Purpose
This randomized phase III trial is studying whole-brain radiation therapy and stereotactic radiosurgery with or without temozolomide or erlotinib to see how well they work compared to whole-brain radiation therapy and stereotactic radiosurgery in treating patients with brain metastases secondary to non-small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by blocking blood flow to the tumor. It is not yet known whether radiation therapy and stereotactic radiosurgery are more effective with or without temozolomide or erlotinib in treating brain metastases
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Tumors Metastatic to Brain |
Drug: erlotinib hydrochloride Radiation: 3-dimensional conformal radiation therapy Radiation: stereotactic radiosurgery Drug: temozolomide |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Trial Comparing Whole Brain Radiation And Stereotactic Radiosurgery Alone Versus With Temozolomide Or Erlotinib In Patients With Non-Small Cell Lung Cancer And 1-3 Brain Metastases |
- Overall Survival [ Time Frame: From randomizaton to date of death for last follow-up. Analysis occurs after all patients have been potentiall followed for 9 months. ] [ Designated as safety issue: No ]Survival time is defined as time from randomization to date of death from any cause and estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact.
- Time to CNS Progression [ Time Frame: From the date of randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: No ]CNS progression will be defined as any increase in perpendicular bi-dimensional tumor area for any of the 1-3 tracked brain metastases, by any amount, or the appearance of any new brain metastasis on a follow-up MRI (SRS planning scan will not be used to evaluate CNS progression).
- Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after the primary outcome analysis. ] [ Designated as safety issue: No ]Compared between two treatment arms using a two-group t-test.
- Change in Functional Assessment of Cancer Therapy-Brain Subscale Questionnaire [ Time Frame: From randomization to three months. ] [ Designated as safety issue: No ]Compared between two treatment arms using a two-group chi-squared test.
- Change in Performance Status [ Time Frame: From randomization to six months. ] [ Designated as safety issue: No ]Compared between two treatment arms using a two-group chi-squared test.
- Change in Steroid Dependence [ Time Frame: From randomization to six months. ] [ Designated as safety issue: No ]Compared between two treatment arms using a two-group chi-squared test.
- Cause of Death (Neurologic vs Other) [ Time Frame: From randomization to date of death. ] [ Designated as safety issue: No ]Compared between two arms using a two-group chi-squared test. Summarized in a 2x2 frequency table.
| Enrollment: | 381 |
| Study Start Date: | October 2004 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: WBRT + SRS
Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery (SRS).
|
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy
|
|
Experimental: WBRT + SRS + Temozolomide
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
|
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy
Drug: temozolomide
Given orally
Other Names:
|
|
Experimental: WBRT + SRS + Erlotinib
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
|
Drug: erlotinib hydrochloride
Given orally
Other Names:
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Compare survival in patients with non-small cell lung cancer and brain metastases treated with whole brain radiotherapy and stereotactic radiosurgery with vs without temozolomide or erlotinib.
SECONDARY OBJECTIVES:
I. Compare time to CNS progression in patients treated with these regimens. II. Compare quality-adjusted survival in patients treated with these regimens. III. Compare 3-month quality of life in patients treated with these regimens. IV. Compare the 6-month performance status of patients treated with these regimens.
V. Compare 6-month steroid dependence in patients treated with these regimens. VI. Compare cause of death (neurologic vs other) in patients treated with these regimens.
VII. Determine the effects of non-protocol chemotherapy in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age and the presence of extracranial metastases (< 65 years old AND no extracranial metastases vs ≥ 65 years old OR extracranial metastases), number of metastases (1 vs 2 or 3), and extent of extracranial disease (none vs present). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
ARM II: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM III: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
In all arms, patients with recurrent brain metastases may undergo additional stereotactic radiosurgery.
Quality of life is assessed at baseline and at 3, 6, 9, 12, 18, and 24 months.
Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically confirmed non-small cell lung cancer
One to 3 intraparenchymal brain metastases by contrast-enhanced MRI, meeting the following criteria:
- Well circumscribed tumor(s)
Maximum diameter ≤ 4.0 cm
- If multiple lesions are present and one lesion is at the maximum diameter, the other lesions must be ≤ 3.0 cm in maximum diameter
- No metastases within 10 mm of the optic apparatus such that a portion of the optic nerve or chiasm would be included in the high-dose stereotactic radiosurgery boost field
- No metastases in the brainstem, midbrain, pons, or medulla
No prior complete resection of all known brain metastases
- Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter
No clinical or radiographic evidence of progression (other than study lesion[s]) within the past month
- Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease
Stable extracranial metastases allowed
- No known or pre-existing liver metastases
- No leptomeningeal metastases by MRI or cerebrospinal fluid evaluation
- Synchronous brain metastases at initial diagnosis allowed
- Performance status - Zubrod 0-1
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- AST < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 2 times ULN unless due to elevated bone metastases
- Total bilirubin normal
- Lactic dehydrogenase < 2 times ULN
- Creatinine < 1.5 times ULN
No clinically active interstitial lung disease
- Chronic stable asymptomatic radiographic changes allowed
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Neurologic function status 0-2
- No other major medical illness or psychiatric impairment that would preclude study participation
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to erlotinib or temozolomide
- No concurrent immunotherapy
- No concurrent biologic therapy, excluding growth factors and epoetin alfa
- No prior temozolomide or erlotinib
No other concurrent chemotherapy during study radiotherapy
Other concurrent chemotherapy allowed after study radiotherapy, except for the following:
- Temozolomide or erlotinib (arm I only)
- Erlotinib (arm II only)
- Temozolomide (arm III only)
- No prior cranial radiotherapy
- No concurrent intensity-modulated radiotherapy
Concurrent radiotherapy to painful bone lesions allowed
- No concurrent radiotherapy to more than 15% of bone marrow
- No other concurrent therapy for brain metastases unless a recurrence is detected
- More than 30 days since prior investigational drugs
No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following (for patients randomized to receive erlotinib):
- Phenytoin
- Carbamazepine
- Rifampin
- Phenobarbital
- Primidone
- Oxcarbazepine
- No other concurrent investigational drugs
- No concurrent Hypericum perforatum (St. John's wort)
- No drugs that alter gastric pH (e.g., proton pump inhibitors or H2 antagonists) within 4 hours after erlotinib administration (arm III patients only)
Contacts and Locations
Show 56 Study Locations| Principal Investigator: | Paul Sperduto | American College of Radiology Imaging Network |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00096265 History of Changes |
| Other Study ID Numbers: | NCI-2009-00720, RTOG-0320, U10CA021661, CDR0000389490 |
| Study First Received: | November 9, 2004 |
| Results First Received: | March 5, 2013 |
| Last Updated: | March 5, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Neoplasm Metastasis Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Neoplastic Processes |
Pathologic Processes Temozolomide Dacarbazine Erlotinib Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Protein Kinase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013