Non-small Cell Lung Cancer
Conditions
Keywords
STARS, Early Stage Non Small Cell Lung Cancer, NSCLC, CyberKnife, Surgery, Accuray
Brief summary
Lung cancer remains the most frequent cause of cancer death in both men and women in the world. Surgical resection using lobectomy with mediastinal lymph node dissection or sampling has been a standard of care for operable early stage NSCLC. Several studies have reported high local control and survival using SBRT in stage I NSCLC patients. SBRT is now an accepted treatment for medically inoperable patients with stage I NSCLC and patients with operable stage I lung cancer are entered on clinical protocols. The purpose of this study is to conduct a phase III randomized study to compare CyberKnife SBRT with surgery, the current standard of care for stage I operable NSCLC.
Detailed description
Objectives: Primary Goal: To compare overall survival at 3 years. Secondary goals: 1. To compare disease specific survival at 3 years. 2. To compare 3 year progression free survival at the treated primary tumor site 3. To compare grade 3 and above acute and/or chronic toxicities. 4. To evaluate predictive value of pre and post treatment PET scan in clinical outcome.
Interventions
RADIATIONCyberKnife Stereotactic Radiotherapy
Central lesion dose/fractionation: 15 Gy x 4 fractions = 60 Gy; Peripheral lesion dose/fractionation: 20 Gy x 3 fractions = 60 Gy
PROCEDURESurgery
Both open thoracotomy and video assisted thoracotomy (VATS) are acceptable procedures. Surgery may consist of a lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the operative findings
Sponsors
M.D. Anderson Cancer Center
Accuray Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological confirmation of non-small cell cancer will be required by either biopsy or cytology. The following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma with or without BAC features, large cell carcinoma with or without neuroendocrine features, neuroendocrine carcinoma, bronchioloalveolar cell carcinoma, or non-small cell carcinoma not otherwise specified. 2. Eligible patients must have appropriate staging studies identifying them as specific subsets of the revised IASCL state IA or IB based on only one of the following combinations of TNM staging: T1, N0, M0 or T2 (\<=4 cm), N0, M0 3. A PET/CT scan is required. Patients with hilar or mediastinal lymph nodes with short axis diameter \< 1 cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with \> 1 cm short axis diameter of hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsy of all abnormally identified areas are negative for cancer. Solitary pulmonary lesions \<4 mm will not be considered significant. 4. The patients must be considered a reasonable candidate for surgical resection of the primary tumor. Standard justification for deeming a patient medically operable based on pulmonary function for surgical resection of NSCLC may include any of the following: Baseline FEV1 \> 40% predicted, post-operative predicted FEV1 \> 30% predicted, diffusion capacity \> 40% predicted, absent baseline hypoxemia and/or hypercapnia, exercise oxygen consumption \> 50% predicted, absent severe pulmonary hypertension, absent severe cerebral, cardiac, or peripheral vascular disease, and absent severe chronic heart disease. 5. Patients must be ≥ 18 years of age. 6. The patient's Zubrod performance status must be Zubrod 0-2. 7. Mandatory staging studies: Must be done within 8 weeks prior to study entry 8. Patients must sign a study-specific consent form. 9. Patients (men and women) of child bearing potential should use an effective (for them) method of birth control throughout their participation in this study.
Exclusion criteria
1. Patients with primary tumors \> 4 cm; 2. Patients with well-differentiated neuroendocrine carcinoma (carcinoid tumor) 3. Direct evidence of regional or distant metastases after appropriate staging studies, or synchronous primary or prior malignancy in the past 5 years other than nonmelanomatous skin cancer or in situ cancer; 4. Previous lung or mediastinal radiotherapy; 5. Plans for the patient to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) while on this protocol except at disease progression; 6. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus; 7. Cannot achieve acceptable SRT planning to meet minimal requirement of target coverage and dose-volume constraints of critical structures (see RT techniques).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 3 years | The study power was calculated for sample size of 420 patients, enrolled over 7 years. The actual enrollment was 36 patients over 4 years. The study was therefore terminated due to lack of enrollment. The sample size does not allow to analysis of the primary outcome. While the study data is not mature enough to evaluate the endpoints of the study, we will attempt to describe the results gleaned from the existing patient population. |
Countries
China, France, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CyberKnife Stereotactic Radiotherapy CyberKnife Stereotactic Radiotherapy: Central lesion dose/fractionation: 15 Gy x 4 fractions = 60 Gy; Peripheral lesion dose/fractionation: 20 Gy x 3 fractions = 60 Gy | 20 |
| Surgery Surgery: Both open thoracotomy and video assisted thoracotomy (VATS) are acceptable procedures. Surgery may consist of a lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the operative findings | 16 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | not treated on study arm | 11 | 11 |
| Overall Study | study closed | 19 | 14 |
Baseline characteristics
| Characteristic | CyberKnife Stereotactic Radiotherapy | Surgery | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 10 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 6 Participants | 14 Participants |
| Age, Continuous | 67.5 years STANDARD_DEVIATION 10.4 | 67.8 years STANDARD_DEVIATION 9.9 | 67.7 years STANDARD_DEVIATION 9.9 |
| ECOG/Zubrod performance status 0 | 14 participants | 12 participants | 26 participants |
| ECOG/Zubrod performance status 1 | 5 participants | 4 participants | 9 participants |
| ECOG/Zubrod performance status 2 | 0 participants | 0 participants | 0 participants |
| ECOG/Zubrod performance status 3 | 0 participants | 0 participants | 0 participants |
| ECOG/Zubrod performance status 4 | 0 participants | 0 participants | 0 participants |
| ECOG/Zubrod performance status 5 | 0 participants | 0 participants | 0 participants |
| ECOG/Zubrod performance status Missing | 1 participants | 0 participants | 1 participants |
| Lesion Type Central | 4 participants | 4 participants | 10 participants |
| Lesion Type Peripheral | 16 participants | 12 participants | 26 participants |
| Primary Tumour stage T1a | 11 participants | 10 participants | 18 participants |
| Primary Tumour stage T1b | 5 participants | 5 participants | 13 participants |
| Primary Tumour stage T2a | 4 participants | 1 participants | 5 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 19 | 2 / 14 |
| other Total, other adverse events | 7 / 20 | 2 / 16 |
| serious Total, serious adverse events | 0 / 20 | 2 / 16 |
Outcome results
Primary
Overall Survival
The study power was calculated for sample size of 420 patients, enrolled over 7 years. The actual enrollment was 36 patients over 4 years. The study was therefore terminated due to lack of enrollment. The sample size does not allow to analysis of the primary outcome. While the study data is not mature enough to evaluate the endpoints of the study, we will attempt to describe the results gleaned from the existing patient population.
Time frame: 3 years
Population: At the time of study closure, 20 patients were treated on the CyberKnife arm and 16 on the Surgery arm. Two deaths were captured on the Surgery arm during the course of the study and one patient enrolled on the CyberKnife arm passed away before being treated with CyberKnife.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CyberKnife Stereotactic Radiotherapy | Overall Survival | 19 Participants |
| Surgery | Overall Survival | 14 Participants |
Post Hoc
Patient Characteristics
While the study data is not mature enough to evaluate the endpoints of the study, we will attempt to describe the results gleaned from the existing patient population.
Time frame: 3 years
Population: No patients randomized in either treatment arm made it to 3 years follow-up. No further data was collected or will be collected on the patient population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Age: 50-59 | 1 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Male | 10 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Pts enrolled at MD Anderson | 12 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Female | 10 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Age: 60-69 | 8 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Age: 40-49 | 2 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Peripheral Tumor | 16 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Age: 70-79 | 7 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | T1a | 11 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Pts enrolled from other sites | 8 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | T1b | 5 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Age: 80-89 | 2 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | T2a | 4 Participants |
| CyberKnife Stereotactic Radiotherapy | Patient Characteristics | Central Tumor | 4 Participants |
| Surgery | Patient Characteristics | T2a | 1 Participants |
| Surgery | Patient Characteristics | Pts enrolled at MD Anderson | 10 Participants |
| Surgery | Patient Characteristics | Pts enrolled from other sites | 6 Participants |
| Surgery | Patient Characteristics | Age: 40-49 | 0 Participants |
| Surgery | Patient Characteristics | Age: 50-59 | 3 Participants |
| Surgery | Patient Characteristics | Age: 60-69 | 8 Participants |
| Surgery | Patient Characteristics | Age: 70-79 | 2 Participants |
| Surgery | Patient Characteristics | Age: 80-89 | 3 Participants |
| Surgery | Patient Characteristics | Male | 7 Participants |
| Surgery | Patient Characteristics | Female | 9 Participants |
| Surgery | Patient Characteristics | Central Tumor | 4 Participants |
| Surgery | Patient Characteristics | Peripheral Tumor | 12 Participants |
| Surgery | Patient Characteristics | T1a | 10 Participants |
| Surgery | Patient Characteristics | T1b | 5 Participants |