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EGF-R Positive Non-Small Cell Lung CancerCULTRONCT05998993

Study to Evaluate SBRT for EGFR Mutant NSCLC Patients Receiving Osimertinib (CULTRO)

A study testing Stereotactic Body Radiation Therapy SBRT in people with EGF-R Positive Non-Small Cell Lung Cancer and Non Small Cell Lung Cancer, run by Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo at 1 site in Colombia.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Phase II Study to Evaluate the Impact of SBRT (Stereotactic Body Radiation Therapy) and/or SRS (Stereotactic Radiosurgery) on Oligoresidual Disease in EGFR Mutation Patients Treated with Osimertinib as First-Line Systemic Intervention. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Stereotactic Body Radiation Therapy SBRT
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteColombia
Study dates
Nov 2023to Nov 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be older than 18 years of age.
  • Be capable of giving informed consent to participate in the study.
  • Have histological confirmation compatible with EGFR mutant non-small cell lung cancer (NSCLC) and metastatic disease (with or without histological confirmation of metastatic lesions).
  • Have confirmation of the presence of common EGFR mutations (exon 19 deletion, L858R/exon 21, or G719X) through any locally and internationally accepted standard tests.
  • Have received at least 12 weeks of Osimertinib treatment (with or without the addition of chemotherapy based on FLAURA2 study results after discussion with the investigative team).
  • Have a partial response defined by RECIST 1.1 criteria.
Show all 27Show fewer
  • Have a maximum of 5 residual tumor lesions in up to 2 organs suitable for treatment with Stereotactic Ablative Radiotherapy (SABR).
  • Have the following imaging and clinical tests within 4 weeks before study entry:
  • Contrast-enhanced brain MRI.
  • Chest/abdomen/pelvis CT scan, with or without bone scan (at the investigator's discretion) if PET-CT was not performed.
  • 18-FDG PET-CT.
  • Spinal MRI for patients with vertebral or paravertebral metastases.
  • Electrocardiogram (EKG) and transthoracic echocardiogram.
  • Complete blood count and standard blood chemistry.
  • Negative pregnancy test for fertile women within 4 weeks prior to starting radiotherapy.
  • Liquid biopsy for assessment of tumor allelic fraction (baseline).
  • ECOG performance status 0-2.
  • All sites of oligoresidual disease must be safely treatable according to the following criteria:
  • All brain lesions must be treatable with SRS.
  • The maximum size for extracranial lesions will be up to 6 cm, with exceptions for bone metastases which may include lesions larger than 6 cm at the discretion of the investigative medical team (e.g., ribs, scapula, or pelvis).
  • Life expectancy >6 months.
  • Not eligible for surgical treatment.
  • Osimertinib treatment must be suspended 48 hours before the start of ablative therapy and cannot be initiated within 48 hours of receiving the last fraction. In patients receiving SBRT for central lung lesions, the suspension time for Osimertinib may be extended up to 5 days before and after ablative therapy.
  • Patients may have previously received treatments such as radiofrequency or microwave ablation for oligoresidual lesions, but imaging must demonstrate that the lesion persists and is treatable with SABR.
  • Metastatic tumor lesions that received initial treatment with radiosurgery cannot be included for SABR treatment.
  • If initial treatment was conventional radiotherapy, SABR could be considered if safe to administer. In this case, the ablative therapy must be discussed by the investigative team.
  • The eligibility and prognosis criteria will be reviewed by the multidisciplinary thoracic tumor board at CTIC Centro de Tratamiento e Investigación Sobre Cáncer Luis Carlos Sarmiento Angulo.

Who cannot join

  • Severe comorbidities contraindicating radiation therapy.
  • Bone metastases in the femur with a high risk of fracture.
  • Complete response to Osimertinib treatment (no oligoresidual disease for ablative treatment).
  • Inability to treat all oligoresidual lesions with ablative intent.
  • History of pneumonitis or functionally limiting interstitial lung disease. It may be considered limiting if the patient is unable to perform DLCO maneuvers or if adjusted DLCO is less than 35% of predicted, PaO2 at Bogotá altitude with FiO2 21% is less than or equal to 50 mmHg.
  • Clinical or radiological evidence of symptomatic spinal cord compression.
Show all 12Show fewer
  • Dominant brain metastatic disease requiring surgical management (e.g., imminent herniation or hydrocephalus).
  • Candidate for a clinical trial with an experimental drug.
  • Inability to receive Osimertinib with minimal adherence.
  • Oligoresidual involvement in peritoneum, pleura, or bone marrow (non-measurable disease).
  • Leptomeningeal involvement (presumed based on imaging findings or confirmed by cerebrospinal fluid cytology).
  • Pregnant or breastfeeding women.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Liliana Gutiérrez, RN contact

3003768158

lgutierrez@fctic.org

Briegel De Las Salas, Microb contact

3044921963

bcalderon@fctic.org

Colombia1 site

  • CTIC - Centro de Tratamiento e Investigación Sobre Cáncer Luis Carlos Sarmiento Angulo

    Bogotá

    Liliana Gutiérrez, RN, 573003768158, lgutierrez@fctic.org

    Briegel De Las Salas, Microb, 573044921963, bcalderon@fctic.org

Other trials in Colombia

About this study

Official title: Phase II Study to Evaluate the Efficacy and Safety of SBRT as an Adjunctive Intervention for Oligoresidual Disease in EGFR Mutant NSCLC With First-Line Osimertinib Treatment

Phase II Study to Evaluate the Impact of SBRT (Stereotactic Body Radiation Therapy) and/or SRS (Stereotactic Radiosurgery) on Oligoresidual Disease in EGFR Mutation Patients Treated with Osimertinib as First-Line Systemic Intervention. All candidates must exhibit a partial response after 12 weeks of treatment with the third-generation tyrosine kinase inhibitor (alone or in combination with chemotherapy) and a maximum of five (5) residual lesions in a maximum of two (2) organs. The primary outcome will be progression-free survival (PFS), and secondary outcomes will include overall survival (OS), proportion of patients without progression at months 12 and 36, safety, and overall response rate (ORR). Additionally, an exploratory analysis will be conducted on the prognostic value of liquid biopsy (supplementary information), considering baseline presence of mutations (determined by Next Generation Sequencing tests) and reduction or negativization of allelic fraction (AF).

Read the detailed description

Phase II study with a single-stage Fleming design based on a normal approximation to the binomial distribution, with a one-sided type I error of 10% and a power of 90% to detect 30 events related to disease progression. Under the alternative hypothesis to detect a 35% improvement in PFS, 35 patients are required to be recruited over 22 months, with a minimum median follow-up of 14 months. An interim analysis will be conducted to determine early termination of the study using a Lan-DeMets monitoring boundary and an O'Brien-Fleming stopping rule. The interim analysis will be performed when 20 out of the expected 30 events have been observed. Employing the O'Brien-Fleming statistic, the critical value for the Z-score in the interim analysis (to stop and reject the null hypothesis) will be 1.054, and the critical value for the Z-score to stop and reject the alternative (futility) will be -0.204.

Being tested
Stereotactic Body Radiation Therapy SBRT
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stereotactic Body Radiation Therapy SBRTRadiation

    Also called Stereotactic radiosurgery SRS

    This is a non-randomized Phase II study in which all patients receive the experimental treatment with Stereotactic Ablative Radiotherapy (SABR) to residual tumor lesions (up to 5 residual metastatic lesions in a maximum of 2 organs) following 12 weeks of systemic treatment with Osimertinib. The study aims to enroll 35 patients diagnosed and treated at CTIC Centro de Tratamiento e Investigación Sobre Cáncer Luis Carlos Sarmiento Angulo.

Study groups in NCT05998993
Study groupRoleWhat they receive
RadiationExperimentalA total of 35 patients diagnosed and treated at CTIC Centro de Tratamiento e Investigación Sobre Cáncer Luis Carlos Sarmiento Angulo.
Receives: Radiation: Stereotactic Body Radiation Therapy SBRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival

    Time from the initiation of systemic treatment (Osimertinib) to disease progression or death. This outcome is not influenced by second-line interventions and allows for the estimation of the relative efficacy of the treatment and its Hazard Ratio (HR)

    Measured: Month 12

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    Proportion of patients with partial or complete response following the implementation of SBRT. This measurement does not include stable disease

    Measured: Month 12

  2. Overall Survival (OS)

    Time from diagnosis, the first day of systemic treatment, and implementation of SBRT to death from any cause or last follow-up

    Measured: Month 12

  3. Progression-Free Time (PFT)

    Time from the execution of SBRT to objective tumor progression, excluding death

    Measured: Month 12

  4. Adverse Events and Safety

    Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5 from the National Cancer Institute (NCI) US

    Measured: Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2023
  2. Study startNov 2023 (estimated)
  3. Primary completionNov 2026 (estimated)
  4. Study completionNov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05998993
Sponsor's protocol ID
CTIC001
Acronym
CULTRO
Status last verified
Aug 2023
First submitted
28 Jul 2023
Last updated
21 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The current study is intended to be published, even if prematurely terminated. The publication may encompass all or part of the following variations: online publication of a synopsis, abstract and/or presentation at a scientific conference, or publication of a complete scientific article.

Publications

  • Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S; ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237. doi: 10.1093/annonc/mdy275. No abstract available.

    PubMed 30285222

  • Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MCL, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-1889. doi: 10.1093/annonc/mdv270. Epub 2015 Jun 23.

    PubMed 26105600

  • Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. doi: 10.1016/S1470-2045(11)70184-X. Epub 2011 Jul 23.

    PubMed 21783417

  • Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. doi: 10.1016/S1470-2045(09)70364-X. Epub 2009 Dec 18.

    PubMed 20022809

  • Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005 Feb 24;352(8):786-92. doi: 10.1056/NEJMoa044238.

    PubMed 15728811

  • Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.

    PubMed 21135146

  • Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 2013 Apr 15;19(8):2240-7. doi: 10.1158/1078-0432.CCR-12-2246. Epub 2013 Mar 7.

    PubMed 23470965

  • Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3.

    PubMed 24893891

  • Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. doi: 10.1200/JCO.2018.77.9363. Epub 2018 Jul 30.

    PubMed 30059262

  • Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. doi: 10.1016/S1470-2045(16)30508-3. Epub 2016 Oct 14.

    PubMed 27751847

  • Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, Blackhall F, Haggstrom D, Yoh K, Novello S, Gold K, Hirashima T, Lin CC, Mann H, Cantarini M, Ghiorghiu S, Janne PA. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol. 2017 Apr 20;35(12):1288-1296. doi: 10.1200/JCO.2016.70.3223. Epub 2017 Feb 21.

    PubMed 28221867

  • Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

    PubMed 27959700

  • Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

    PubMed 29151359

  • Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21.

    PubMed 31751012

  • Al-Halabi H, Sayegh K, Digamurthy SR, Niemierko A, Piotrowska Z, Willers H, Sequist LV. Pattern of Failure Analysis in Metastatic EGFR-Mutant Lung Cancer Treated with Tyrosine Kinase Inhibitors to Identify Candidates for Consolidation Stereotactic Body Radiation Therapy. J Thorac Oncol. 2015 Nov;10(11):1601-7. doi: 10.1097/JTO.0000000000000648.

    PubMed 26313684

Questions about this trial

What is this clinical trial studying?

A study testing Stereotactic Body Radiation Therapy SBRT in people with EGF-R Positive Non-Small Cell Lung Cancer and Non Small Cell Lung Cancer, run by Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo at 1 site in Colombia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Liliana Gutiérrez, RN (3003768158, lgutierrez@fctic.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (time frame: Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05998993, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.

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