A Phase II Trial Evaluating Upfront Stereotactic Body Radiotherapy in Stage III Advanced Non-small Cell Lung Cancer (APRIL)

April 30, 2026 updated by: Aman Sharma, All India Institute of Medical Sciences

The APRIL Trial: A Phase II Trial Evaluating Upfront Stereotactic Body Radiotherapy in Stage III Advanced Non-small Cell Lung Cancer

The aim of the study is to test the feasibility & loco-regional control rate by combining high precision SBRT with chemotherapy in stage III NSCLC in tumor/lymph nodes if tumors/lymph node size with ≤ 6cms in size.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The standard of care for unresectable stage III NSCLC lung cancer is combination chemoradiotherapy and best results are achieved when radiation is given along with concurrent chemotherapy [1]. Concurrent chemoradiotherapy (CRT) is associated an overall survival rate at 5 years between 15%-32% [1,2].

Local relapse in stage III NSCLC can vary from 20% to 50% [1-3]. Conventional radiation therapy results in high local failure rates that theoretically could act as a nidus for metastasis [1,3]. For NSCLC, there is a proposed dose effect on local control and survival with doses of at least 70 Gy and tumors with volumes >100 cc require higher doses for better local control [3]. However, in a prospective randomised controlled trial setting, CRT dose escalation with conventional radiotherapy was associated with inferior local control, PFS, OS and higher toxicity [2].

Stereotactic body radiotherapy (SBRT) delivers high dose conformal radiation through multiple radiation beams with steep dose gradients in 3-8 fractions and has shown limited toxicity despite delivering a high dose BED10>100 in early NSCLC. Local control in early-stage NSCLC with SBRT is around 85-90% [5, 6]. Ohnishi et al. in their landmark paper demonstrated significant survival benefits for stage I lung cancer with SBRT doses of biological equivalent (BED)10 in excess of 100 Gy[5]. SBRT with BED10>100 Gy has convincingly achieved excellent treatment out comes in early-stage NSCLC [7]. Similar local control may be achieved SBRT in stage III NSCLC provided safe dose of BED10>100 Gy is delivered. This holds true when tumor diameter is ≤ 6 cms.

SBRT has been combined with conventional CRT in stage III NSCLC with intent to decrease local failure. A recently conducted systematic review of SBRT in inoperable stage III NSCLC has published SBRT outcomes [8].In this systematic review, 6 studies considered SBRT administration in stage III NSCLC, 1 employed SBRT in monotherapy and 5 employed SBRT as dose escalation after conventional chemoradiotherapy [8]. Median dose of conventional radiotherapy was 50.4 Gy in 28 fractions and median dose of SBRT boost was 22.25 Gy in 2 to 7 fractions. SBRT was used to treat primary tumor and involved lymph nodes in 3 out of 5 studies. The systematic review concluded that dose-escalation with 2 fraction SBRT (20-24 Gy) was feasible and was associated with local control rate of 78% at 1 year with 3.7% grade 5 and 14.2% grade 3toxicity [8].

There is data emerging on use of SBRT as monotherapy in stage III NSCLC [9, 10]. Yang et al treated ultra-central tumors with SBRT to primary and lymph nodes to a dose of 35 Gy in 5 fractions. Despite large tumors (median tumor diameter was 6.8 cm [range: 2.1-12.4 cms] and ultra-central location median local control was 17 months for stage III patients. Grade 3 or higher toxicity was observed in 9.8% of patients [9]. Another phase II trials examined the feasibility of SBRT is locally advanced NSCLC[10]. The prescribed doses were 30 Gy/5daily fractions at the reference isodose (60-70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. Median follow-up was 87 months (range: 6-87), local PFS was 19.8 months (95% CI 9.7 - not reached), OS was 23 months. Late toxicity was represented by 24% dyspnea G3.

Hilar/mediastinal SBRT is a safe technique for isolated nodal disease [11-13]. A retrospective study that treated 40 patients of NSCLC with SBRT for primary/oligorecurrent hilar/mediastinal lymph nodes. The median dose of SBRT was 48 Gy in 4 fractions. The aortico-pulmonary window was the target in 40%, hilum in 25%, lower paratracheal in 20%, subcarinal in 10%, and prevascular in 5%. Acute grade 3+ morbidity was seen in 3 patients (hemoptysis, pericardial/pleural effusion, heart failure) and late grade 3+ morbidity (hemoptysis) in 1 patient[11].A systematic review of SBRT on mediastinal & hilar lymph nodes that included 196 patients has been recently conducted [13]. Non-small cell lung cancer (NSCLC) was the most common primary (65%) tumor subjected to mediastinal & hilar node SBRT. The reported dose and fractionation ranged from 21 Gy to 60 Gy in 3-11 fractions, with median BED ranged from 46-106 Gy. SBRT was associated with excellent local control (LC) rates of 69%-97% & 1 year OS of 69%-75%. Pooled grade 3-5 toxicity rate according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 was 6% (n=11). Pooled SABR-related mortality (grade 5 toxicity) rate was 2% (n=4). Three SABR-related deaths from esophageal fistulae (2 to trachea, 1 to mediastinum) were reported, with all 3 having prior RT to the subcarinal nodes [13].

Given the safety & excellent efficacy of SBRT for small tumors (≤ 6cms) as well as hilar & medistinal lymph nodes, the present phase study is designed evaluate SBRT in stage III NSCLC.

References

  1. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181-2190,
  2. Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG oncology RTOG 0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable Stage III non-small-cell lung cancer. J Clin Oncol. 2020; 38:706-714.
  3. McGarry RC. Integrating stereotactic body radiation therapy in stage II/III non-small cell lung cancer: is local control important? Expert Rev Anticancer Ther2014; 14:1419-27.
  4. Willner J, Baier K, Caragiani E, et al. Dose, volume and tumor control predictions in primary radiotherapy of non-small cell lung cancer. Int J Rad Oncol Biol Phys 2002;52: 382-9.
  5. Onishi H, Araki T, Shirato H, Nagata Y, et al. Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multi-institutional study. Cancer 2004; 101: 1623-31.
  6. Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010; 303: 1070-6.
  7. Zhang J, Yang F, Li B, et al. Which is the optimal biologically effective dose of stereotactic body radiotherapy for Stage I non-small-cell lung cancer? A meta-analysis. Int J Radiat Oncol Biol Phys 2011; 81: e305-16.
  8. Alcibar OL, Nadal E, Palomar IR, et al. Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer. Transl Lung Cancer Res 2021;10(1):529-538.
  9. Cong Y, Sun B, Wang J, et al. Outcomes and toxicity of stereotactic body radiation therapy for advanced stage ultra-central non-small cell lung cancer. Thoracic Cancer 2019;10:1567-1575.
  10. Parisi E, GenestretiG ,Sarnelli A, et al. Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up. Radiation Oncology 2019 14:112.
  11. Horne ZD, Richman AH, Dohopolski MJ, Clump DA, Burton SA, Heron DE. Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers. Lung Cancer. 2018;115:1-4.
  12. Meng MB, Wang HH, Zaorsky NG, et al., Clinical evaluation of stereotactic radiation therapy for recurrent or second primary mediastinal lymph node metastases originating from non-small cell lung cancer, Oncotarget 6 (17) (2015)15690-15703
  13. Tjong MC, Malik NH, Hanbo Chen H, et al. Stereotactic ablative radiotherapy for malignant mediastinal and hilar lymphadenopathy: a systematic review. J Thorac Dis 2020;12(5):2280-2287
  14. Brunt AD, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. The Lancet 2020;395 (10237):1613-26.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • India
    • Haryana
      • Jhajjar, Haryana, India, 124105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Aged 18 or above and less than 75 years.
  2. Histologically proven non-small cell lung cancer.
  3. Stage T1-4, N1-3, M0 with maximum tumor size less than 6 cms and ≤ 3 stations of largest lymph node size less than 4 cms.
  4. ECOG status 0-1.
  5. Available to attend long term follow- up.
  6. Written informed consent for treatment.

Exclusion Criteria:

  1. Metastatic disease.
  2. Tumor size > 6cm.
  3. Involved Lymph node size greater than 4 cms & more than 3 station of lymph nodes involved.
  4. Patients with superior vena cava obstruction.
  5. Tumor invading/encasing the proximal bronchial tree/, esophagus, pericardium.
  6. Previous radiotherapy to thorax.
  7. Small cell histology.
  8. Age< 18 or > 75 years.
  9. Patients on anticoagulant therapy & ultra-central cavitary tumors.
  10. Poor performance status ECOG 2-3.
  11. Immunocompromised states.
  12. Viral Markers negative.
  13. Pregnant women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SBRT in stage III NSCLC
The study will evaluate efficacy & toxicity of SBRT in stage III NSCLC
Radiation: SBRT in stage III NSCLC
SBRT to primary tumor and lymph nodes in stage III NSCLC when gross disease is < 6 cms

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Loco-regional control rate
Time Frame: 2 years
Loco regional control rate assessment till 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease free survival
Time Frame: 2 years
Longitudinal assessment every 2 months for initial six months and every 3 months till next 2 years
2 years
Overall survival
Time Frame: 2 years
Longitudinal assessment every 2 months for initial six months and every 3 months till next 2 years
2 years
CTCAE V5 Toxicity
Time Frame: 2 years

CTCAE Grades

Grade refers to the severity of the adverse event. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL*.

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**.

Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Assessed at base line, post SBRT, post Chemotherapy, first follow up, at 6 months and then 6 monthly
2 years
EORTC QLQ C30 Quality of life
Time Frame: 2 years

The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.

Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. High score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Assessed at base line, post SBRT, post Chemotherapy, first follow up, at 6 months and then 6 monthly
2 years
EORTC LC-13 Quality of life
Time Frame: 2 years

The lung cancer module incorporates one multi-item scale to assess dyspnoea, and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis. It has scoring system from 1 to 4, higher score represents higher symptom burden.

Assessed at base line, post SBRT, post Chemotherapy, first follow up, at 6 months and then 6 monthly
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
All India Institute of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • The APRIL Trial

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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