Radical Resection Vs. Ablative Stereotactic Radiotherapy in Patients With Operable Stage I NSCLC

NCT01753414 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: RF-3502
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Alive Without Local-regional Failure at Two Years (Local-regional Tumor Control)

  Local-regional failure (LRF) is defined differently for each arm. LRF after RODS is defined as recurrence, defined by CT, confirmed by PET/CT whenever possible, i.e., development of tumor masses at site of resection, hilum (N1 nodal region), mediastinum (N2-N3 nodes), ipsilateral supraclavicular fossa for upper lobe tumors (N3 nodes), or within 3 cm of the staple line of RODS. LRF after SBRT is defined as tumor progression on CT per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, confirmed by positron PET/CT, within same lobe, hilum (N1 nodes), mediastinum (N2-N3 nodes), or ipsilateral supraclavicular fossa for upper lobe tumors (N3 nodes), or within 3 cm of original planning target volume (PTV). Local-regional control time is defined as time from randomization to the date of first LRF, death, or last known follow-up (censored), whichever occurred first. Rates are estimated using the Kaplan-Meier method.

  From date of randomization to two years

Secondary Outcomes (11)

• Overall Survival (Percentage of Participants Alive)

  From date of randomization to date of death or last follow-up. Maximum follow-up was 7.0 years.

• Percentage of Participants With Local-regional Failure (LRF)

  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.

• Percentage of Participants With Distant Failure

  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.

• Percentage of Participants Alive Without Disease [Disease-free Survival (DFS)]

  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.

• Number of Participants by Failure Site

  From date of randomization to date of last known follow-up. Maximum follow-up was 7.0 years.

Study Arms (2)

Surgery

OTHER

R0 resection (radical resection) with nodal dissection or sampling (RODS).

Procedure: Surgery

Stereotactic Body Radiation Therapy (SBRT)

EXPERIMENTAL

Stereotactic Body Radiation Therapy (SBRT) given every other day 11 Gy in 5 fractions to a total dose of 55 Gy in 10-15 days with an inter-fraction interval of 2-3 days.

Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Daily fractions

Stereotactic Body Radiation Therapy (SBRT)

Surgery PROCEDURE

Radical resection

Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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%;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• Varian Medical Systems: collaborator

Study Sites (4)

Chinese Academy of Medical Science

Beijing, 10021, China

Location

Shandong Cancer Hospital, Jinan

Shangdong, 250117, China

Location

Shanghai Cancer Center/Fudan University

Shanghai, 200032, China

Location

Zhejiang Cancer Hospital, Hangzhou

Zhejiang, 310022, China

Location

Related Publications (1)

• 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.

  PMID: 32736936 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Radiosurgery; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Investigative Techniques

Limitations and Caveats

This study stopped accrual early due to unmet targeted accrual goals with 44 participants randomized out of 72 planned. Statistical testing was not done due to low accrual.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

2155743208

Study Officials

• Feng-Ming (Spring) Kong, MD, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: December 20, 2012
• Study Start: December 1, 2012
• Primary Completion: April 3, 2023
• Study Completion: January 1, 2026
• Last Updated: January 6, 2025
• Results First Posted: January 6, 2025

Record last verified: 2024-04

Locations

CN (4)