Non-small Cell Lung Cancer Metastatic, Targetable Oncogenes (EGFR, ALK, ROS1)
Conditions
Keywords
Non-small cell lung cancer, Metastatic, EGFR, ALK, ROS1, Stereotactic Body Radiation Therapy
Brief summary
This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS proto-oncogene 1 (ROS1) gene (= oncogene-driven NSCLC) and for which the subject has been receiving treatment with a targeted biological agent such as erlotinib, crizotinib, or other drugs.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. The investigational intervention in this study is SBRT with proton or photon radiation (explained below). Investigational means that the intervention is being studied. SBRT and proton radiation therapy are FDA approved radiation delivery systems. However, using it as a treatment for stage IV NSCLC is still investigational. SBRT is a specialized, technologically advanced type of external beam radiation therapy that pinpoints high doses of radiation directly on the cancer. Because of high precision, these treatments spare healthy tissue and are associated with fewer side effects. SBRT is very different from conventional therapy where radiation is delivered in small doses given daily over the course of several weeks. For SBRT, the total dose of radiation is typically administered in 4-5 daily sessions. SBRT can be delivered with standard, so called photon radiation, or proton beam. Neither of these two types of radiation is generally superior over the other. There are technical differences between these two, and depending on tumor location, size, shape, and other factors, the investigators will decide which type of radiation to use for which treatment. After the screening procedures confirm you are eligible to participate in the research study: \- Each participant will receive stereotactic treatment course (SBRT with protons or photons) to the area of their tumor.
Interventions
RADIATIONSBRT with protons or photons
Sponsors
National Cancer Institute (NCI)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with any actionable mutation or translocation in EGFR, ALK, or ROS1 * Stage IV disease (AJCC Staging system 7th edition) * Within 6 months of initiating their first TKI treatment regimen * Stable or responding systemic disease to TKI (no evidence of progression) on the most recent staging studies. The complete extent of the current residual systemic disease must be deemed amenable to SBRT as per review of imaging studies by a radiation oncologist, based on the following criteria: * Lung: 1-3 lesions (including the primary) of maximum size 5 cm in longest diameter. A minimum size 1 cm in the longest diameter is recommended. (Patients with a malignant pleural effusion prior to the start of TKI therapy will be considered eligible for SBRT if there is complete radiographic resolution of the effusion while on systemic therapy); * Spine: Bone lesions must be limited to the spine. A maximum of 2 spinal metastases will be considered for SBRT, with each site spanning 1-3 vertebral bodies. A minimum size of 1 cm in longest diameter is recommended. SBRT may target sclerotic lesions that persist following TKI therapy; * GI: 1-4 liver metastases of maximum size 5 cm in longest diameter and/or 1-2 adrenal metastases of maximum 4 cm size in longest diameter. A minimum size of 1 cm in longest diameter is recommended. In addition: * CNS: 1-4 brain metastases of maximum size 3cm in longest diameter. However, these should be treated with standard-of-care SRS and will not be defined as target lesions for purposes of this protocol. * A maximum number of 5 target lesions outside the brain, excluding the lung primary, is recommended to ensure that enrollment is limited to patients with low-burden disease and that treatments can be delivered within the specified time frame. * History of prior radiation therapy to brain or skeleton is allowed, but should have occurred \> 2 months from enrollment. * Age at least 18 years. * Life expectancy of greater than 6 months. * ECOG performance status ≤ 2. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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. A negative serum or urine pregnancy test within 2 weeks of registration for women of childbearing potential is required. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Residual hilar or mediastinal lymph node disease (size \> 1cm in short-axis diameter on CT). Non-malignant etiologies for enlarged lymph nodes may be evaluated per standard clinical practice. * Participants who have received prior radiation therapy to anatomical sites other than brain or skeleton. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients who are pacemaker or defibrillator-dependent as these devices may not be operated concurrently with delivery of proton beam radiation. * Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT) | 1 year | Distant failures (DF) are defined as metastases outside areas that originally contained disease. The 1-year frequency of DF is defined as the percentage of patients that experienced a DF, respectively, over the course of one year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT) | Up to 8.4 years | Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE v4.0). Treatment-related toxicities are defined as adverse events assessed as related to SBRT. |
| Median Progression Free Survival | Up to 7.65 years | Progression free survival is defined as the duration of time from the start of standard of care TKI (tyrosine kinase inhibitor) therapy until objective progressive disease or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Median Overall Survival | Up to 8.4 years | Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death. |
| 2-year Overall Survival | 2 years | Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death. The 2-year overall survival is defined as the percentage of participants who were alive 2 years after the start of documented tyrosine kinase inhibitor (TKI) therapy. |
| 2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT) | 2 years | Local failure is defined as progressive disease in target lesions treated with SBRT. The 2-year LF rate is the percentage of participants who experienced local failure within 2 years of completing SBRT. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Body Radiation Therapy (SBRT) With Protons or Photons * SBRT dosage determined by treating physician
* Patients will continue to receive standard of care (SOC) tyrosine kinase inhibitors (TKI) in the intervals between SBRT courses, as well as after the completion of SBRT
* If there is more than one active site of cancer, additional site(s) will be treated with stereotactic treatment courses. The total duration of SBRT courses (from the first day of any SBRT course to the last day of any SBRT course) will not exceed 4 months. | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Stereotactic Body Radiation Therapy (SBRT) With Protons or Photons |
|---|---|
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT)
Distant failures (DF) are defined as metastases outside areas that originally contained disease. The 1-year frequency of DF is defined as the percentage of patients that experienced a DF, respectively, over the course of one year.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | 1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT) | 19 percentage of participants |
Secondary
2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT)
Local failure is defined as progressive disease in target lesions treated with SBRT. The 2-year LF rate is the percentage of participants who experienced local failure within 2 years of completing SBRT.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | 2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT) | 11 percentage of participants |
Secondary
2-year Overall Survival
Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death. The 2-year overall survival is defined as the percentage of participants who were alive 2 years after the start of documented tyrosine kinase inhibitor (TKI) therapy.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | 2-year Overall Survival | 88 percentage of participants |
Secondary
Median Overall Survival
Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death.
Time frame: Up to 8.4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | Median Overall Survival | 59.6 months |
Secondary
Median Progression Free Survival
Progression free survival is defined as the duration of time from the start of standard of care TKI (tyrosine kinase inhibitor) therapy until objective progressive disease or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Up to 7.65 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | Median Progression Free Survival | 23.4 months |
Secondary
Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT)
Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE v4.0). Treatment-related toxicities are defined as adverse events assessed as related to SBRT.
Time frame: Up to 8.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT) | 0 Participants |