Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Lung Cancer, Proton Radiotherapy, Proton Beam, NSCLC
Brief summary
The goal of this clinical research study is to learn if escalated/accelerated proton radiotherapy can improve the control of Non-Small Cell Lung Cancer (NSCLC) and decrease side effects. The safety of this treatment will also be studied. Objectives: To assess the therapeutic efficacy and toxicities of proton radiotherapy with escalated/accelerated dose for patients with medically inoperable stage I (T1-2, N0,M0) NSCLC. Primary goals: 1. Improve 2 years progression free survival at the primary site, and 2. reduce acute and chronic toxicity Secondary goals: 1. Improve disease specific survival at 2 years. 2. Study the potential of pre- and post treatment PET/CT in predicting clinical outcome. 3. Study the role of biomarkers in predicting therapeutic response and toxicities.
Detailed description
A proton beam is made up of charged particles that have a well-defined range of penetration into tissues. How deep it can penetrate is decided by both the beam's energy and the density of the tissue through which it passes. As the proton beam penetrates the body, the particles slow down, and the beam deposits its dose sharply near the end of its range. This is a phenomenon known as the Bragg peak. By adjusting the Bragg peak, the doctor can deliver a full, localized, uniform dose of energy to the treatment site while sparing the surrounding normal tissues. The proton beam is ideal for treatments where organ preservation is very important, such as lung cancer. Researchers know that standard photon radiotherapy is not able to adequately control tumor growth. But unfortunately, it is not possible to increase the dose of photon radiotherapy without also significantly increasing the side effects. In this study, using proton radiotherapy, researchers will increase the dose about 40% higher than standard photon radiotherapy. Screening Tests Signing this consent form does not mean that you will be able to take part in this study. You will have screening tests to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed before starting treatment on this study: Your complete medical history will be recorded. You will have a physical exam. Blood (about 4 teaspoons) will be drawn (within 30 days) for the routine blood tests You will have a computed tomography (CT) scan or positron emission tomography (PET/CT) scan of the chest, an MRI scan or CT of the brain, You will have a lung function test. Women who are able to have children must have a negative blood-pregnancy test. You will have a 4DCT. Study Drug Administration If you are found to be eligible to take part in this study, you will receive 35 treatments of proton radiotherapy (radiotherapy does not have to start on a Monday but it cannot start on a Friday; usually Monday through Thursday for 7 to 8 weeks). During the treatment, you will lie still on a table for about 30-45 minutes per day in the same position. The proton machine will deliver the dose according to the plan designed by the physician and controlled by a computer. You will not feel, see, or smell anything during the proton beam delivery. During the treatment, you will be seen by a doctor and research nurse once a week to evaluate possible side effects. You will have a physical exam and you will have a medical history. You will be taken off study early if the disease gets worse or intolerable side effects occur. After finishing the treatment, follow up is recommended 6 weeks after completion of radiotherapy, required every 3 months (+/-1 month) for two years, then every (+/-1 month) 6 months for three years, and then once a year for 2 years. You will have imaging tests (chest CT or PET scan), lung function test and routine blood tests (about 2 teaspoons) at the follow-up visits. You are allowed to have further chemotherapy or other treatment while you are still in the follow-up on this study. You should discuss chemotherapy with your medical oncologist. This is an investigational study. Proton radiotherapy is FDA approved for the treatment of lung cancer treatment. Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
RADIATIONProton Radiotherapy
87.5 CGE with 2.5 Gy/fraction for 35 treatments
Sponsors
National Cancer Institute (NCI)
Massachusetts General Hospital
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically documented NSCLC. 2. Patients with inoperable centrally located tumors, defined as those within 2 cm of the bronchial tree, major vessels, esophagus, heart, or other mediastinal structures but no direct invasion, T1N0M0 (stage IA), or any location of T2N0M0 (stage IB) and T3N0M0 (selected stage II with chest wall involvement) NSCLC. 3. Performance score KPS 60-100.
Exclusion criteria
1. Prior radiotherapy to the chest. 2. Previous or concomitant malignancy other than (a) curatively treated carcinoma in situ of cervix, (b) basal cell carcinoma of the skin, (c) curatively treated superficial transitional cell carcinoma of the urinary bladder, and (d) early stage tumor treated more than 3 years ago for cure. 3. Pregnancy. Patients, both men and women of child bearing potential should use an effective method of birth control throughout their participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival and Progression Free Survival | The Overall survival (OS): time of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): time of registration to any local-regional recurrence or distant metastasis up to 5 years. | Chest CT with contrast (if possible) was used for evaluation of Local control. If is suspicious for recurrence by CT image, PET or PET/CT scan is required and biopsy is recommended to confirm the recurrence. Continuing CT or PET images follow up for un-confirmed recurrent disease. Timing of recurrence: at the time of first image (PET and/or CT) showing abnormalities. PET will use for progression free survival (PFS). Participants were followed up at 6 weeks after the completion of RT, every 3 months (±1 month) for 2 years, every 6 months (±1 month) for 3 years, and then annually. The Overall survival: time of registration to the last follow-up (f/u), or lost to f/u, or death. The PFS: time of registration to any local-regional recurrence or distant metastasis. Free local recurrence rate: time of registration to local recurrence. Free regional recurrence rate: time of registration to regional recurrence. Free distant metastasis rate: time of registration to distant metastasis. |
Countries
United States
Participant flow
Recruitment details
(1)Inoperable NSCLC;(2)T1N0M0 (stage IA) that was centrally or superiorly located ≤ 2 cm in all directions of any critical mediastinal structure; T2N0M0 in any location (stage IB, tumor size\>3 cm, with no upper size limit), or selected T3N0M0 (stage II,chest wall, mediastinal pleura, or parietal pericardium involvement) in any location (3)ECOG≤2
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l 35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10 | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Dose-escalated Proton Therapy for Early-stage Non-small Cell l |
|---|---|
| Age | 73 years |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Chronic Pulmonary Disease COPD | 16 Participants |
| Chronic Pulmonary Disease Emphysema | 3 Participants |
| Chronic Pulmonary Disease Normal | 15 Participants |
| Chronic Pulmonary Disease Pulmonary Fibrosis | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gross Tumor Volume (GTV) | 42.9 cubic centimeters |
| iCTV (internal Clinical Target Volume) | 123 cubic centimeters |
| Karnofsky Performance Status (KPS) Score | 80 units on a scale (%) |
| Number of Participants with Clinical Stage IA | 12 participants |
| Number of Participants with Clinical Stage IB | 16 participants |
| Number of Participants with Clinical Stage IIA | 4 participants |
| Number of Participants with Clinical Stage IIB | 3 participants |
| Number of Participants with Primary Tumor (T) Stage T1:Tumor ≤3 cm in greatest dimension | 12 participants |
| Number of Participants with Primary Tumor (T) Stage T2:tumor>3 cm; involve: main bronchus, the viscera | 20 participants |
| Number of Participants with Primary Tumor (T) Stage T3 | 3 participants |
| Number of Participants with Tumor Location Central or Superior | 25 Participants |
| Number of Participants with Tumor Location Peripheral | 10 Participants |
| Number of Participants with Tumor size ≤3 cm | 13 participants |
| Number of Participants with Tumor size >3 cm ≤ 5 cm | 16 participants |
| Number of Participants with Tumor size >5 cm | 6 participants |
| Pre-Treatment Pulmonary Function - DLCO | 49 percentage of predicted (%) |
| Pre-Treatment Pulmonary Function - FEV1 | 48 percentage of predicted (%) |
| Region of Enrollment United States | 35 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 17 Participants |
| Smoking History No | 4 Participants |
| Smoking History Yes | 31 Participants |
| Tumor Histological Type Adenocarcinoma | 11 Participants |
| Tumor Histological Type Neuroendocrine carcinoma | 1 Participants |
| Tumor Histological Type Non-small cell carcinoma | 5 Participants |
| Tumor Histological Type Squamous cell carcinoma | 17 Participants |
| Tumor Histological Type Squamous cell carcinoma + adenocarcinoma | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 35 |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 2 / 35 |
Outcome results
Primary
Overall Survival and Progression Free Survival
Chest CT with contrast (if possible) was used for evaluation of Local control. If is suspicious for recurrence by CT image, PET or PET/CT scan is required and biopsy is recommended to confirm the recurrence. Continuing CT or PET images follow up for un-confirmed recurrent disease. Timing of recurrence: at the time of first image (PET and/or CT) showing abnormalities. PET will use for progression free survival (PFS). Participants were followed up at 6 weeks after the completion of RT, every 3 months (±1 month) for 2 years, every 6 months (±1 month) for 3 years, and then annually. The Overall survival: time of registration to the last follow-up (f/u), or lost to f/u, or death. The PFS: time of registration to any local-regional recurrence or distant metastasis. Free local recurrence rate: time of registration to local recurrence. Free regional recurrence rate: time of registration to regional recurrence. Free distant metastasis rate: time of registration to distant metastasis.
Time frame: The Overall survival (OS): time of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): time of registration to any local-regional recurrence or distant metastasis up to 5 years.
Population: Kaplan-Meier curves used for overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival. Differences between pairs of Kaplan-Meier curves were using the log-rank test. The Fisher's exact test was used to compare local, regional, and distant recurrence rates.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Overall Survival rate : 1 year | 85.70 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Overall Survival rate : 2 year | 60 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Overall Survival rate : 3 year | 42.90 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Overall Survival rate : 5 year | 28.10 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Progression Free Survival rate : 1 year | 80 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Progression Free Survival rate : 2 year | 64.40 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Progression Free Survival rate : 3 year | 53.60 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | Progression Free Survival rate : 5 year | 53.60 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | free local recurrence rate 5-year | 85 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | free from regional recurrence rate: 5-year | 89.20 percentage of participants (%) |
| Dose-escalated Proton Therapy for Early-stage Non-small Cell l | Overall Survival and Progression Free Survival | free from distant metastasis rate: 5-year | 56 percentage of participants (%) |