Clinical trial NCT01753414: Radical Resection Vs. Ablative Stereotactic Radiotherapy in Patients With Operable Stage I NSCLC
Official title: POSTILV: A RANDOMIZED PHASE II TRIAL IN PATIENTS WITH OPERABLE STAGE I NON-SMALL CELL LUNG CANCER: RADICAL RESECTION VERSUS ABLATIVE STEREOTACTIC RADIOTHERAPY - This is a Limited Participation Study.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Lung Cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: Varian Medical Systems
First posted: 2012-12-20
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale: Surgery remains the standard of care for stage 1 (T1-2a N0)non-small cell lung cancer. Stereotactic body radiation therapy is a newer radiation treatment that gives fewer but higher and possibly more effective doses of radiation than standard radiation. This technique may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery in treating non-small cell lung cancer.

Purpose: The primary aim of this randomized phase II trial is to determine if the efficacy of SBRT is comparable to that of standard surgical interventions for patients with T1N0 non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

- Pathologically (histologically or cytologically) proven diagnosis of Stage I NSCLC \[American Joint Committee on Cancer (AJCC), 7th ed.\], T1N0M0; note: T1N0 disease must be confirmed by FDG-PET/CT. (FDG = 18F-fluorodeoxyglucose; PET = positron emission tomography; CT = Computed Tomography)

Biopsy confirmation of diagnosis is strongly recommended but not required. If the biopsy is attempted and non-diagnostic, if the patient refuses biopsy, or if the risk of biopsy is considered too high, patients may be enrolled if the mass is suspicious for NSCLC based on 2 or more of the following criteria:

* Positive smoking history;
* Absence of benign calcifications within suspicious nodule;
* Activity on PET greater than normal tissue;
* Evidence of growth compared to previous imaging;
* Presence of spiculation.

The following primary cancer types are eligible: squamous cell carcinoma; adenocarcinoma; large cell carcinoma/ large cell neuroendocrine carcinoma; non-small cell carcinoma not otherwise specified.

* Patients with hilar or mediastinal lymph nodes ≤ 1 cm and no abnormal hilar or mediastinal uptake on PET and CT will be considered N0. Mediastinal lymph node biopsy is required for patients with visible nodes: patients with \> 1 cm hilar or mediastinal lymph nodes on CT or with nodes appearing as abnormal on PET (including suspicious but nondiagnostic uptake). Such patients will not be eligible unless directed biopsies of all abnormal lymph nodes are negative for cancer or these nodes demonstrate a lack of change during the prior 6 months and thus are considered to be non-malignant.
* The patient must be considered a reasonable candidate for surgical resection using a lobectomy or pneumonectomy of the primary tumor within 6 weeks prior to registration, according to the following criteria based on the American College of Chest Physicians guidelines \[165\]:

  * A qualified thoracic surgeon should make the determination that there would be a high likelihood of negative surgical margins;
  * Baseline forced expiratory volume in 1 second (FEV1) \>60% predicted, postoperative predicted FEV1 \>40% predicted;
  * Diffusion capacity of the lung for carbon monoxide (DLCO) \>60% predicted, postoperative predicted DLCO \> 40 % predicted;
  * No baseline hypoxemia and/or hypercapnia;
  * If the estimated postoperative FEV1 or DLCO \<40% predicted indicates an increased risk for perioperative complications, including death, from a standard lung cancer resection (lobectomy or greater removal of lung tissue), then cardiopulmonary exercise testing to measure maximal oxygen consumption (VO2max) must be \>60%;
  * No severe pulmonary hypertension;
  * No severe cerebral, acute or chronic cardiac, or peripheral vascular disease;
* Pleural effusion, if present, must be deemed too small to tap under CT guidance and must not be evident on chest x-ray. Pleural effusion that appears on chest x-ray will be permitted only if there is no evidence of malignancy after invasive cytologic assessment.
* Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

  * History/physical examination, including documentation of weight within 6 weeks prior to registration;
  * Evaluation by an experienced thoracic surgeon within 6 weeks prior to registration;
  * FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
  * CT scan (preferably with intravenous contrast, unless medically contraindicated) within 4 weeks prior to registration to include the entirety of both lungs, the mediastinum, liver, and adrenal glands; primary tumor dimension will be measured on CT scan.
* Zubrod Performance Status 0-1 within 6 weeks prior to registration;
* Age ≥ 18;
* For women of childbearing potential, a serum or urine pregnancy test must be negative within 72 hours prior to registration;
* Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment if assigned to treatment with SBRT.
* Patients must provide study specific informed consent prior to study entry.

Exclusion Criteria:

* Direct evidence of regional or distant metastases after PET and surgical staging studies, or synchronous primary malignancy or prior invasive malignancy in the past 3 years, with the following exceptions:

  * carcinoma in situ;
  * early stage skin cancer that has been definitively treated;
  * when an invasive malignancy has been treated definitively and the patient has remained disease free for ≥ 3 years;
* Primary tumors \>3 cm;
* Prior systemic chemotherapy or thoracic surgery involving lobectomy or pneumonectomy;
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
* Pure bronchioloalveolar carcinoma subtype of non-small cell lung cancer;
* Active systemic, pulmonary, or pleural pericardial infection;
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

Primary outcomes:
measure: Percentage of Participants Alive Without Local-regional Failure at Two Years (Local-regional Tumor Control)
timeFrame: From date of randomization to two years
Secondary outcomes:
measure: Overall Survival (Percentage of Participants Alive)
timeFrame: From date of randomization to date of death or last follow-up. Maximum follow-up was 7.0 years.
measure: Percentage of Participants With Local-regional Failure (LRF)
timeFrame: From date of randomization to the date of first local-regional failure, death, or last known follow-up, whichever occurred first. Maximum follow-up is 7.0 years.
measure: Percentage of Participants With Distant Failure
timeFrame: From date of randomization to date of first distant failure, death, or last known follow-up, whichever occurred first. Maximum follow-up was 7.0 years.
measure: Percentage of Participants Alive Without Disease [Disease-free Survival (DFS)]
timeFrame: From date of randomization to the date of first failure, death, or last known follow-up, whichever occurred first. Maximum follow-up is 7.0 years.
measure: Number of Participants by Failure Site
timeFrame: From date of randomization to date of last known follow-up. Maximum follow-up was 7.0 years.
measure: Best PET Tumor Response
timeFrame: From date of randomization to date of last known follow-up. Maximum follow-up was 7.0 years.
measure: Number of Participants by Highest Grade Adverse Event Reported
timeFrame: From date of randomization to the date of last known follow-up. Maximum follow-up time was 7.0 years.
measure: Number of Participants With Surgical and Radiation Treatment Credentialing Completed and Documented Before Enrollment (Trial Feasibility)
timeFrame: baseline
measure: Number of Eligible Participants (Trial Feasibility)
timeFrame: Baseline
measure: Number of Participants With Baseline Forms Completed and Provided Within 30 Days of Randomization (Trial Feasibility)
timeFrame: Baseline
measure: Number of Participants Lost to Follow-up (Trial Feasibility)
timeFrame: From date of randomization to date of last known follow-up. Maximum follow-up was 7.0 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Science
city: Shangdong
country: China
facility: Shandong Cancer Hospital, Jinan
city: Shanghai
country: China
facility: Shanghai Cancer Center/Fudan University
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital, Hangzhou
Study officials:
affiliation: Case Western Reserve University
name: Feng-Ming (Spring) Kong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.