Summary:
Patients with stage I non-small cell lung cancer have been historically treated with surgery whenever they are fit for an operation. However, an alternative treatment known as stereotactic radiotherapy now appears to offer an equally effective alternative. Doctors believe both are good treatments and are therefore conducting this study to determine if one may be possibly better than the other.
ClinicalTrials.gov Identifier: NCT02984761
Recruitment Status: Recruiting
First Posted: December 7, 2016
Last Update Posted: September 13, 2022
Sponsor:
VA Office of Research and Development
Information provided by (Responsible Party):
VA Office of Research and Development
Detailed Description:
The standard of care for stage I non-small cell lung cancer has historically been surgical resection in patients who are medically fit to tolerate an operation. Recent data now suggests that stereotactic radiotherapy may be a suitable alternative. This includes the results from a pooled analysis of two incomplete phase III studies that reported a 15% overall survival advantage with stereotactic radiotherapy at 3 years. While these data are promising, the median follow-up period was short, the results underpowered, and the findings were in contradiction to multiple retrospective studies that demonstrate the outcomes with surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two treatments in a prospective randomized fashion with a goal to compare the overall survival beyond 5 years. It has been designed to enroll patients who have a long life-expectancy and are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node sampling.
This study is designed to open at Veterans Affairs medical centers with expertise in both treatments. The recruitment process includes shared decision making and multi-disciplinary evaluations with lung cancer specialists. Mandatory evaluations before randomization include tissue confirmation of NSCLC, staging with FDG-PET/CT, and biopsies of all hilar and/or mediastinal lymph nodes >10mm that have a SUV >2.5. Pre-randomization elective lymph node sampling is strongly encouraged, but not required. Following treatment, patients will be followed for a minimum of 5 years.
Study Design
Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 670 participants.
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CSP #2005 – Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy Trial (VALOR)
Actual Study Start Date: April 13, 2017
Estimated Primary Completion Date: September 30, 2026
Estimated Study Completion Date: September 30, 2027
Primary Outcome Measures:
Safety and tolerability of IK-930 [ Time Frame: Through study completion, an average of 36 months ]
The frequency and severity, incidence of treatment-emergent and treatment-related adverse events using NCI-CTCAE v5.0
Occurrence of Dose Limiting Toxicity during first treatment cycle [ Time Frame: Approximately 1 year ]
RP2D and/or MTD of IK-930 [ Time Frame: Approximately 1 year ]
Define the recommended phase 2 dose (RP2D) and/or MTD of IK-930
Secondary Outcome Measures:
Antitumor activity per RECIST 1.1: Disease control rate (DCR) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Antitumor activity per RECIST 1.1: Time to response (TTR) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Antitumor activity per RECIST 1.1: Duration of response (DOR) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Antitumor activity per RECIST 1.1: Objective response rate (ORR) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Antitumor activity: Median progression-free survival (PFS) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Antitumor activity: Median overall survival (OS) of IK-930 as a single agent [ Time Frame: Through study completion, average of 36 months ]
Pharmacokinetics of IK-930: half-life (t1/2) [ Time Frame: Approximately 1 year ]
Pharmacokinetics of IK-930: Area Under the Curve (AUC) [ Time Frame: Approximately 1 year ]
Pharmacokinetics of IK-930: Maximum Plasma Concentration (Cmax) [ Time Frame: Approximately 1 year ]
Pharmacokinetics of IK-930: Minimum Plasma Concentration (Cmin) [ Time Frame: Approximately 1 year]
Criteria
Inclusion Criteria for Screening
- Age 18 or older
- Any patient with a preliminary diagnosis of stage I Non-Small Cell Lung Cancer (NSCLC), whether pathologically proven by biopsy, or highly suspicious by radiographic imaging. [Participants will need biopsy confirmation before enrolling]
- Primary tumor size less than or equal to 5 cm by CT (may include CT images from PET/CT)
- Karnofsky performance status greater than or equal to 70
- Participant has willingness and ability to provided informed consent for participation.
Inclusion Criteria for Randomization
- Biopsy proven non-small cell lung cancer.
- Participant’s case reviewed at multidisciplinary conference.
- Tumor size less than or equal to 5cm (measured on the most recent CT images available, and may include PET/CT images)
- Tumor is equal to or greater than 1.0cm from the trachea, esophagus, brachial plexus, 1st bifurcation of the proximal bronchial tree, or spinal cord (measured on the most recent CT images available and may include PET/CT images).
- Mandatory FDG-PET/CT within 60 days of the randomization date (note: FDG-PET/CT may need to be repeated prior to treatment if outside of this requirement)
- Mandatory pathological assessment of any lymph nodes >10mm with a SUV >2.5 seen on FDG- PET/CT
- Mandatory biopsy of any additional concerning lesions seen on FDG-PET/CT, to make better determination that the patient is not harboring metastatic disease or a secondary primary malignancy.
- Pre-operative FEV1 greater than or equal to 40% of predicted value and pre-operative DLCO greater than or equal to 40% of predicted value.
- Formally evaluated and documented by a local thoracic surgeon to be medically fit to undergo a complete anatomic pulmonary resection (wedge resection not allowed)
- Formally evaluated and documented by a local radiation oncologist to be eligible to receive protocol-defined stereotactic radiotherapy.
- Participant willingness to be randomized.
Exclusion Criteria for Screening
- Previously evaluated by a local thoracic surgeon and determined to be medically inoperable
- Pathological confirmation of nodal or distant metastasis
- Prior history of lung cancer, not including current lesion
- Prior history of thoracic surgery or lung or esophageal cancer. [prior cardiac surgery acceptable]
- Prior history of radiotherapy to the thorax
- Prior history of an invasive malignancy within the past 5 years, whether newly diagnosed or recurrent, excluding low-risk prostate cancer, non-melanoma skin cancers, and in-situ cancers
- Ever diagnosed with stage IV metastatic cancer of any type
- History of scleroderma
- Positive Pregnancy test (for women <61 years of age or without prior hysterectomy)
Exclusion Criteria for Randomization
- Pathological confirmation of nodal or metastatic disease
Contacts
Contact: Robert Cameron, MD | (310) 794-7333 | robert.cameron@va.gov
Contact: Diane Gage, MD | (310) 478-3711 | Diane.Gage@va.gov
Locations:
VA Long Beach Healthcare System, Long Beach, CA: Recruiting
Long Beach, California, United States, 90822
Contact: Bahman Saatian, MD | 562-826-5591 | bahman.saatian@va.gov
Contact: Gelincik K Orakcilar, MS | 562-826-8000 ext. 24172 | gelincik.orakcilar@va.gov
VA Greater Los Angeles Healthcare System, West Los Angeles, CA: Recruiting
West Los Angeles, California, United States, 90073
Contact: Drew Moghanaki, MD MPH | 804-306-9045 | Drew.Moghanaki@va.gov
Contact: Vicki L Skinner, RN | (894) 675-5105 | vicki.skinner@va.gov
Study Chair: Drew Moghanaki, MD MPH
For more locations: See Contacts and Locations
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Elbanna M, Shiue K, Edwards D, Cerra-Franco A, Agrawal N, Hinton J, Mereniuk T, Huang C, Ryan JL, Smith J, Aaron VD, Burney H, Zang Y, Holmes J, Langer M, Zellars R, Lautenschlaeger T. Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy. Clin Lung Cancer. 2021 May;22(3):e342-e359. doi: 10.1016/j.cllc.2020.05.024. Epub 2020 Jun 2.
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02984761 History of Changes
Other Study ID Numbers: 2005
First Posted: December 7, 2016, Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022
