NCT03110978

Brief Summary

This phase II trial studies how well stereotactic body radiation therapy with or without nivolumab works in treating patients with stage I-IIA non-small cell lung cancer or cancer that has come back. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy and nivolumab may work better at treating non-small cell lung cancer.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
140

participants targeted

Target at P75+ for phase_2

Timeline
1mo left

Started Jun 2017

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 7, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 12, 2017

Completed
3 months until next milestone

Study Start

First participant enrolled

June 26, 2017

Completed
9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

April 16, 2026

Status Verified

April 1, 2026

Enrollment Period

9 years

First QC Date

April 7, 2017

Last Update Submit

April 13, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Event-free survival with events defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death

    Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis.

    From the randomization date, assessed up to 5 years

Secondary Outcomes (3)

  • Overall survival

    From the randomization date assessed up to 5 years

  • Incidence of adverse events related to stereotactic body radiation therapy and immunotherapy

    Up to 5 years

  • Immunologic markers analyses

    Up to 5 years

Study Arms (2)

Arm I (stereotactic body radiation therapy)

EXPERIMENTAL

Patients undergo stereotactic body radiation therapy over 1-2 weeks.

Radiation: Stereotactic Body Radiation Therapy

Arm II (stereotactic body radiation therapy, nivolumab)

EXPERIMENTAL

Patients undergo stereotactic body radiation therapy over 1-2 weeks. Beginning within 36 hours before or after the first fraction of stereotactic body radiation therapy, patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 4 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Biological: NivolumabRadiation: Stereotactic Body Radiation Therapy

Interventions

NivolumabBIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Arm II (stereotactic body radiation therapy, nivolumab)

Undergo stereotactic body radiation therapy

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Arm I (stereotactic body radiation therapy)Arm II (stereotactic body radiation therapy, nivolumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histological confirmation of non-small cell lung cancer (NSCLC) by either biopsy or cytology is required for the primary diagnosis and is recommended for recurrent disease. The following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma (with or without bronchioloalveolar carcinoma features), large cell carcinoma (with or without neuroendocrine features), neuroendocrine carcinoma (either NSCLC with neuroendocrine features or atypical carcinoids, but not small cell lung carcinoma), bronchioloalveolar cell carcinoma, or non-small cell carcinoma not otherwise specified
  • Stage I or selected stage IIa according to the 7th version of the International Association for the Study of Lung Cancer (IASLC) system: stage I (T1 or T2a \[tumor size =\< 5 cm\] N0M0) stage IIa (T2 \[tumor size \> 5 cm but =\< 7 cm\] N0M0)
  • Patients with multiple primary lung tumors (defined below) are eligible:
  • Synchronous tumors (diagnosed within 6 months \[mo\]),
  • Different histology,
  • Same histology,
  • Second tumor in different lobed or lung;
  • Metachronous tumors (diagnosed \> 6 mo apart),
  • Different histology,
  • Same histology,
  • Second tumor in different lobe or lung,
  • Tumor-free interval of at least 4 years (y)
  • Patient with multiple primary lung tumors who will receive multiple courses of stereotactic body radiation therapy (SBRT) (50Gy in 4Fx or 70Gy in 10Fx) are eligible
  • Patients with isolated lung parenchymal recurrent/persistent NSCLC (histology as defined in eligibility criterion 1) after prior definitive surgery or radiotherapy/chemotherapy, when the lesion or lesions are suitable for SABR, are also eligible.
  • Patients with a single metastatic focus in the lung parenchyma with no other lesions are also eligible, because this presentation is challenging to distinguish from recurrent disease.
  • +28 more criteria

You may not qualify if:

  • Patients with tumors \> 7 cm or tumors involving the main bronchus or associated vessels or tumors that invade any critical structures (such as esophagus, brachial plexus, heart, mediastinal major vessels) are not suitable for SABR
  • Patients with direct evidence of regional or distant metastases after appropriate staging studies, or with synchronous non-lung primary or prior non-lung malignancy (other than nonmelanomatous skin cancer or in situ cancer) diagnosed within the past 3 years are not eligible. Patients with a history of curable non-lung cancer up to 3 years before registration and have been cancer-free for 2 years are eligible
  • Patients who have received previous immunotherapy with PD1 or CTLA4 antibodies are not eligible
  • Patients with plans to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) or other systemic therapy (including chemotherapy, target therapy and other type of immunotherapy or investigative agents) while on this protocol, except at disease progression, are not eligible
  • Female patients who are pregnant or lactating are not eligible (because treatment involves unforeseeable risks to the embryo or fetus)
  • Patients for whom SABR plans cannot meet the minimum requirement of target coverage and dose-volume constraints of critical structures (see SABR treatment planning section) are not eligible
  • Patients who have active, known, or suspected autoimmune disease are not eligible. However, patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition that requires only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Patients with a known history of antibodies to human immunodeficiency virus (HIV) -1 or -2 are not eligible. Patients with live vaccines
  • Patients with a known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection are not eligible
  • Patients who have a condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration are not eligible. However, inhaled or topical steroids, adrenal replacement doses, and \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Patients with allergies or adverse drug reactions to the following are not eligible:
  • History of allergy to study drug components;
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Patients who have had prior treatment with an anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways are not eligible
  • Patients are known to have contraindications to radiotherapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

Related Publications (1)

  • Chang JY, Lin SH, Dong W, Liao Z, Gandhi SJ, Gay CM, Zhang J, Chun SG, Elamin YY, Fossella FV, Blumenschein G, Cascone T, Le X, Pozadzides JV, Tsao A, Verma V, Welsh JW, Chen AB, Altan M, Mehran RJ, Vaporciyan AA, Swisher SG, Balter PA, Fujimoto J, Wistuba II, Feng L, Lee JJ, Heymach JV. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet. 2023 Sep 9;402(10405):871-881. doi: 10.1016/S0140-6736(23)01384-3. Epub 2023 Jul 18.

Related Links

MeSH Terms

Conditions

Adenocarcinoma, Bronchiolo-AlveolarCarcinoma, NeuroendocrineAdenocarcinoma of LungCarcinoma, Non-Small-Cell LungLung Neoplasms

Interventions

NivolumabRadiosurgery

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueCarcinoma, BronchogenicBronchial NeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsRadiotherapyTherapeuticsStereotaxic TechniquesNeurosurgical ProceduresSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Joe Y Chang

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

April 7, 2017

First Posted

April 12, 2017

Study Start

June 26, 2017

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

April 16, 2026

Record last verified: 2026-04

Locations