Non-small Cell Lung Cancer
Conditions
Keywords
radiation therapy, chemotherapy, PET Imaging
Brief summary
The primary objective of this study is to evaluate patient-reported outcomes during and after concurrent chemoradiotherapy for locally-advanced non-small cell lung cancer. Patients will be randomized to a standard 6-week radiotherapy course or a 4-week radiotherapy course using dose-painting based on pre-treatment Positron Emission Tomography (PET) findings.
Detailed description
This study is open for patients with non-small cell lung cancer. This study offers such patients the chance for a shorter and more personalized treatment course utilizing PET imaging. Patients will be stratified based on performance status and tumor size and randomized to one of two treatment plans: 1. PET-based, dose-painted, accelerated chemoradiotherapy over 4 weeks (20 radiotherapy fractions) 2. Standard chemoradiotherapy over 6 weeks (30 radiotherapy fractions) All patients will receive standard weekly doses of chemotherapy (carboplatin and paclitaxel) during radiotherapy. This may be followed by adjuvant systemic therapy, at the discretion of the treating physicians. All patients will undergo standard evaluations prior to enrollment, during treatment, and after treatment. Additionally, patient-reported outcomes will be assessed periodically using a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) tool.
Interventions
COMBINATION_PRODUCTPET-based, dose-painted, accelerated chemoradiotherapy
Patients in this arm will receive a more personalized and shorter radiation therapy treatment course utilizing PET imaging.
COMBINATION_PRODUCTStandard chemoradiotherapy
Patients in this arm will receive a standard radiotherapy course.
Sponsors
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study participants were stratified by performance status (2 vs 0-1) and primary tumor size (\> 4cm or \<= 4cm) and then randomized 1:1 to receive either PET-based, dose-painted radiotherapy or standard radiotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pathologically proven (either histologic or cytologic) diagnosis of NSCLC with any of the following stages according to the American Joint Committee on Cancer (AJCC) Staging Manual, 7th edition, Appendix): * Stage IIIA or IIIB * Stage II NSCLC with contraindication to curative surgical resection * Stage IV disease with solitary brain metastasis that has been treated radically (e.g.: with surgical resection and/or stereotactic radiosurgery) and thoracic disease that would be classified as stage II-III Appropriate diagnostic/staging workup, including: * Complete history and physical examination * PET/CT within 42 days prior to study entry demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s). If PET/CT was obtained more than 42 days prior to study entry and is not repeated, chest CT within 28 days prior to study entry demonstrating stable disease is required. * MRI of the brain or head CT with contrast within 42 days prior to study entry * No prior chemotherapy or thoracic radiotherapy for lung cancer * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Age \> 18 * Able to read and write in one of the following languages, in which the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) tool is available: English, Danish, German, Italian, Japanese, Korean, Spanish * Laboratory studies obtained within 28 days prior to study entry demonstrating adequate bone marrow and end organ function * Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study therapy, agree to utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study therapy is completed, and be advised of the importance of avoiding pregnancy during trial participation and the potential risks of an unintentional pregnancy. All patients must sign study specific informed consent prior to study entry.
Exclusion criteria
* Pleural or pericardial effusion (A patient with pleural effusion may be enrolled the effusion is sampled by thoracentesis and cytology is negative or the effusion is seen on axial imaging but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance.) * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness * Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study therapy * have a positive pregnancy test at baseline * are pregnant or breastfeeding * Poorly controlled diabetes (defined as fasting glucose level \> 200 mg/dL) despite attempts to improve glucose control by fasting duration and adjustment of medications. Patients with diabetes will preferably be scheduled for PET/CT imaging in the morning, and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With PRO-CTCAE Adverse Events With Score ≥ 3 | Up to 6 Weeks after initiation of Chemoradiotherapy | Observation of Grade 3 or higher patient-reported toxicity six weeks after chemotherapy radiation was characterized utilizing the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The PRO-CTCAE is a patient-reported outcome assessment tool developed by the National Cancer Institute (NCI) to capture symptomatic adverse events in patients on cancer clinical trials. Participants completed a customized PRO-CTCAE survey with 24 questions addressing 12 symptoms at baseline, every two weeks during chemoradiotherapy. The number of patients with PRO-CTCAE Grade 3 or higher adverse events was summarized by study arm for each event type. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional Progression-free Survival | Weeks 19, 32, and 45 on study | Locoregional progression-free survival will be evaluated based on repeat imaging and assessed during the interval from study registration to date of local or regional disease progression or death, whichever comes first, censored at the date of data collection |
| Progression-free Survival (PFS) | Weeks 19, 32 and 45 on study | Progression-free survival will be evaluated based on repeat imaging and assessed during the interval from study registration to date of disease progression or death, whichever comes first, censored at the date of data collection. PFS will be summarized by study arm using basic descriptive statistics. |
| Overall Survival (OS) | Up to 45 weeks | Follow ups will be maintained with study patients to determine survival status. OS will be assessed during the interval from study registration to death, censored at the date of data collection. |
| Number of Patients With Grade 3-5 Adverse Events, Scored Using CTCAE Version 4.0 | From treatment start through study week 45 | Evaluation of any Grade 3-5 adverse events, including Grade 3-5 side effects and toxicities, were assessed based on CTCAE Version 4.0. Adverse events/side effects/toxicities have been summarized by study arm. The number/percentage of patients with Grade 3-5 adverse events, scored using CTCAE Version 4.0, is summarized by study arm. |
| Number of Patients With PRO-CTCAE Adverse Events With Score ≥ 3 at Any Time | From treatment start through study week 45 | Evaluation of severe, patient reported side effects or toxicities was assessed. The number/percentage of patients with PRO-CTCAE, scored using CTCAE Version 4.0, is summarized by study arm. |
| Number of Patients With PRO-CTCAE Adverse Events With Any Score | From treatment start through study week 45 | Evaluation of any patient reported side effects or toxicities. This Outcome Measure includes PRO-CTCAE AEs that were Grades 0, 1, or 2. The number of patients with Grade 3 PRO-CTCAE have been summarized in the corresponding Outcome Measure. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNitin Ohri, MD
Montefiore Medical Center
Participant flow
Pre-assignment details
55 patients were consented into the study. 5 patients failed to meet inclusion criteria and were excluded from the study. 50 patients were enrolled and randomized into one of the two study arms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Adjuvant Systemic Therapy Durvalumab | 17 Participants |
| Adjuvant Systemic Therapy None | 6 Participants |
| Adjuvant Systemic Therapy Osimertinib | 2 Participants |
| Age, Continuous | 70 years |
| Clinical Stage Stage II | 1 Participants |
| Clinical Stage Stage IIIA | 23 Participants |
| Clinical Stage Stage IIIB | 18 Participants |
| Clinical Stage Stage IIIC | 3 Participants |
| Clinical Stage Stage IV | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1 | 25 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2 | 8 Participants |
| Histology, Carcinoma Subtype Adenocarcinoma | 23 Participants |
| Histology, Carcinoma Subtype Other/Not Specified | 8 Participants |
| Histology, Carcinoma Subtype Squamous Cell Carcinoma | 9 Participants |
| Metabolic Tumor Volume (MTV) | 48 cubic centimeters |
| Programmed Cell Death Ligand-1 Protein Expression < 50% | 11 Participants |
| Programmed Cell Death Ligand-1 Protein Expression ≥ 50% | 6 Participants |
| Programmed Cell Death Ligand-1 Protein Expression Unknown | 13 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 50 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 27 | 12 / 23 |
| other Total, other adverse events | 27 / 27 | 23 / 23 |
| serious Total, serious adverse events | 4 / 27 | 6 / 23 |
Outcome results
None listed