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Stage III Non-small-cell Lung CancerPhase 2NCT04085250

Study of Nivolumab for Non-Small Cell Lung Cancer (Stage III) Following Neoadjuvant Chemotherapy Plus Nivolumab and Definitive Concurrent Chemoradiation Therapy

A Phase 2 study testing Neoadjuvant therapy, Chemotherapy concurrent with radiotherapy and Radiotherapy in people with Stage III Non-small-cell Lung Cancer, run by Sun Yat-sen University at 3 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The phase II, randomised Study is to explore the efficacy and safety of nivolumab as consolidation therapy in patients with locally advanced, unresectable non-small cell lung cancer (stage III) who have not progressed following neoadjuvant chemotherapy plus nivolumab and definitive concurrent chemoradiation therapy Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Stage III Non-small-cell Lung Cancer
What is being tested?
Neoadjuvant therapy, Chemotherapy concurrent with radiotherapy and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
264 participants
Where
3 sitesChina
Study dates
28 Nov 2019to 31 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For inclusion in neoadjuvant therapy, patients should fulfil the following criteria:
  • Provision of signed, written and dated informed consent prior to any study specific procedures；
  • Male or female aged 18~75 years old；
  • Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease;
  • Without prior chemotherapy, radiotherapy, surgery, targeted therapy or immunotherapy;
  • Tumour sample requirements: Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for analysis;
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  • A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk;
  • Life expectancy ≥12 weeks;
  • World Health Organization (WHO) Performance Status of 0 or 1;
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients within 14 days before the use of study drug (HCG has a minimum sensitivity of 25 IU/L or equivalent);
  • Women must be non-breastfeeding
  • Women of reproductive age (WOCBP) must agree to comply with the contraceptive method during the study nivolumab treatment and for a period of 5 months following the last administration of the study treatment (i.e., 30 days [ovulation cycle] plus approximately 5 half-lives of the study drug).
  • Men who have sex with WOCBP must agree to comply with the contraceptive method during the study nivolumab treatment and for 7 months after the last administration of the study treatment (i.e. 90 days [sperm renewal cycle] plus approximately 5 half-life of the study drug).
  • Spermless men do not have to comply with contraceptive requirements. WOCBP who continues to be asexual with the opposite sex does not have to comply with contraceptive requirements, but must still undergo the pregnancy tests described in this section.
  • Adequate organ and marrow function as defined below:
  • Forced expiratory volume in 1 second (FEV1) ≥800ml
  • Absolute neutrophil count >1.5 x 109/L (1500 per mm3)
  • Platelets >100 x 109/L (100,000 per mm3)
  • Haemoglobin≥9.0 g/dL (5.59 mmol/L)
  • Serum creatinine clearance(CL) >50 mL/min by the Cockcroft-Gault formula (Cockcroft and
  • -Gault 1976)
  • Serum bilirubin ≤1.5 x upper limit of normal (ULN). ··Aspartate Transaminase(AST) and Alanine Transaminase(ALT) ≤2.5 x ULN

Who cannot join

  • Patients should not enter the study if any of the following exclusion criteria are fulfilled:
  • Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
  • Mixed small cell and non-small cell lung cancer histology;
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of Nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
  • Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody;
  • Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of nivolumab;
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  • Active or prior documented autoimmune disease within the past 2 years;
  • Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
  • History of primary immunodeficiency;
  • History of organ transplant that requires therapeutic immunosuppression;
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from3 electrocardiograms (ECGs) using Bazett's Correction;
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
  • Known history of tuberculosis;
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within30 days of receiving nivolumab;
  • History of another primary malignancy within 5 years prior to starting nivolumab, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
  • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control;
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of the nivolumab or interpretation of patient safety or study results.
  • Exclusion criteria for concurrent chemoradiation following neoadjuvant therapy
  • Patients should not enter the concurrent chemoradiation phase if any of the following exclusion criteria are fulfilled:
  • Patients who develop distant metastasis;
  • Patients who develop locoregional disease progression and the irradiation dose of normal tissue will exceed the limit as defined in Section 7.
  • World Health Organization (WHO) Performance Status of 2-4;
  • Inadequate organ and marrow function as defined below:
  • Forced expiratory volume in 1 second (FEV1) <800ml
  • Absolute neutrophil count <1.5 x 109/L (1500 per mm3)
  • Platelets <100 x 109/L (100,000 per mm3)
  • Haemoglobin<9.0 g/dL (5.59 mmol/L)
  • Serum creatinine CL <50 mL/min by the Cockcroft-Gault formula (Cockcroft and
  • Gault 1976)
  • Serum bilirubin >1.5 x upper limit of normal (ULN).
  • Aspartate Transaminase(AST) and Alanine Transaminase(ALT) >2.5 x ULN
  • Further exclusion criteria for randomization into Nivolumab consolidation or observation group
  • Patients should not enter the randomization if any of the following exclusion criteria are fulfilled:
  • Patients who have progressed whilst definitive platinum based, concurrent chemoradiation therapy;
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of Nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
  • Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy will be excluded from randomization;
  • Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded from randomization; Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE>Grade 1.

Trial locations and contacts

3 sites in 1 country.

China3 sites

  • The First People's Hospital of Foshan

    Foshan, Guangdong, 528000

  • Sun yat-sen university cancer center

    Guangzhou, Guangdong, 510000

  • The first affliated hospital of Guangzhou Medical University

    Guangzhou, Guangdong, 510000

Other trials in China

About this study

Official title: A Phase II, Randomised Study of Nivolumab as Consolidation Therapy in Patients With Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Neoadjuvant Chemotherapy Plus Nivolumab and Definitive Concurrent Chemoradiation Therapy

The phase II, randomised Study is to explore the efficacy and safety of nivolumab as consolidation therapy in patients with locally advanced, unresectable non-small cell lung cancer (stage III) who have not progressed following neoadjuvant chemotherapy plus nivolumab and definitive concurrent chemoradiation therapy

Being tested
Neoadjuvant therapy, Chemotherapy concurrent with radiotherapy, Radiotherapy, Nivolumab, Observation
Keywords
Stage III Non-Small Cell Lung Cancer, Neoadjuvant Chemotherapy plus nivolumab, Chemoradiotherapy, Nivolumab consolidation
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.

  • Neoadjuvant therapyOther

    The neoadjuvant therapy before radiotherapy comprised of Docetaxel 60 mg/m2 for 1 hour + Cisplatin 75 mg/m2+Nivolumab 360 mg, once every 3 weeks (Q3W), for a total of 2 cycles.

  • Chemotherapy concurrent with radiotherapyOther

    Docetaxel 25 mg/m2 for 1 hour +Cisplatin 25 mg/m2, once a week (QW)

  • RadiotherapyRadiation

    Hypofractionated radiation technique was used to deliver a definitive radiation dose

  • NivolumabDrug

    Nivolumab consolidation (360 mg) via iv infusion once every 3 weeks (Q3W)±3 days after the neoadjuvant therapy and concurrent chemo-radiotherapy. Administration of nivolumab will commence on Day 1 following randomisation to Nivolumab after confirmation of eligibility and will continue on a Q3W schedule for a maximum duration of 12 months.

  • ObservationOther

    Observation after the neoadjuvant therapy and concurrent chemo-radiotherapy.

Study groups in NCT04085250
Study groupRoleWhat they receive
Nivolumab ConsolidationExperimentalPatients in experimental group will receive Nivolumab consolidation (360 mg) via iv infusion Q3W±3 days after the neoadjuvant therapy and concurrent chemo-radiotherapy.
Receives: Other: Neoadjuvant therapy; Other: Chemotherapy concurrent with radiotherapy; Radiation: Radiotherapy; Drug: Nivolumab
ObservationActive comparatorPatients in this group will receive observation after the neoadjuvant therapy and concurrent chemo-radiotherapy.
Receives: Other: Neoadjuvant therapy; Other: Chemotherapy concurrent with radiotherapy; Radiation: Radiotherapy; Other: Observation

What is being measured

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

  1. Progression-free Survival

    To assess the efficacy of Nivolumab consolidation compared with observation in terms of progression-free survival

    Measured: 2 years

Secondary outcomes (6)

  1. Overall Survival(OS)

    To assess the efficacy of Nivolumab consolidation compared with observation in terms of Overall survival

    Measured: 2 years

  2. Objective Response Rate(ORR)

    To assess the efficacy of Nivolumab consolidation compared with observation in terms of Objective Response Rate; To assess the efficacy of neoadjuvant chemotherapy plus nivolumab in terms of objective response rate after neoadjuvant therapy

    Measured: 2 years

  3. Adverse Event

    To assess the safety of Nivolumab consolidation compared with observation in terms of adverse event

    Measured: 2 years

  4. Symptoms and Health-related Quality of Life

    To assess the symptoms and health-related quality of life in patients treated with Nivolumab consolidation compared with observation

    Measured: 2 years

  5. Progression-free Survival

    To assess the efficacy of neoadjuvant chemotherapy plus nivolumab in terms of progression-free survival for all patients

    Measured: 2 years

  6. Overall Survival

    To assess the efficacy of neoadjuvant chemotherapy plus nivolumab in terms of overall survival for all patients

    Measured: 2 years

Timeline

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

  1. First posted11 Sep 2019
  2. Study start28 Nov 2019
  3. Primary completion31 Jan 2025 (estimated)
  4. Study completion31 Jan 2025 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
264 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04085250
Sponsor's protocol ID
2019-FXY-119
Status last verified
Apr 2024
First submitted
9 Sep 2019
Last updated
23 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

    PubMed 21296855

  • Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: incidence, mortality, survival and prevalence in 2010. Cancer Res Treat. 2013 Mar;45(1):1-14. doi: 10.4143/crt.2013.45.1.1. Epub 2013 Mar 31.

    PubMed 23613665

  • Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L; International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007 Aug;2(8):706-14. doi: 10.1097/JTO.0b013e31812f3c1a.

    PubMed 17762336

  • Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, Carey RW, Frei EF 3rd, Green MR. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990 Oct 4;323(14):940-5. doi: 10.1056/NEJM199010043231403.

    PubMed 2169587

  • Le Chevalier T, Arriagada R, Quoix E, Ruffie P, Martin M, Tarayre M, Lacombe-Terrier MJ, Douillard JY, Laplanche A. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst. 1991 Mar 20;83(6):417-23. doi: 10.1093/jnci/83.6.417.

    PubMed 1847977

  • Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992 Feb 20;326(8):524-30. doi: 10.1056/NEJM199202203260805.

    PubMed 1310160

  • Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. J Clin Oncol. 1996 Apr;14(4):1065-70. doi: 10.1200/JCO.1996.14.4.1065.

    PubMed 8648358

  • Jeremic B, Shibamoto Y, Acimovic L, Djuric L. Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer. J Clin Oncol. 1995 Feb;13(2):452-8. doi: 10.1200/JCO.1995.13.2.452.

    PubMed 7844608

  • Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. doi: 10.1093/jnci/djr325. Epub 2011 Sep 8.

    PubMed 21903745

  • Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. doi: 10.1200/JCO.1999.17.9.2692.

    PubMed 10561343

  • Auperin A, Le Pechoux C, Pignon JP, Koning C, Jeremic B, Clamon G, Einhorn L, Ball D, Trovo MG, Groen HJ, Bonner JA, Le Chevalier T, Arriagada R; Meta-Analysis of Cisplatin/carboplatin based Concomitant Chemotherapy in non-small cell Lung Cancer (MAC3-LC) Group. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients. Ann Oncol. 2006 Mar;17(3):473-83. doi: 10.1093/annonc/mdj117.

    PubMed 16500915

  • Wang Y, Deng W, Li N, Neri S, Sharma A, Jiang W, Lin SH. Combining Immunotherapy and Radiotherapy for Cancer Treatment: Current Challenges and Future Directions. Front Pharmacol. 2018 Mar 5;9:185. doi: 10.3389/fphar.2018.00185. eCollection 2018.

    PubMed 29556198

  • Sacco PC, Maione P, Guida C, Gridelli C. The Combination of New Immunotherapy and Radiotherapy: A N ew Potential Treatment for Locally Advanced Non-Small Cell Lung Cancer. Curr Clin Pharmacol. 2017;12(1):4-10. doi: 10.2174/1574884711666161201123439.

    PubMed 27908252

  • Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

    PubMed 28885881

  • Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

    PubMed 29658848

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoadjuvant therapy, Chemotherapy concurrent with radiotherapy and Radiotherapy in people with Stage III Non-small-cell Lung Cancer, run by Sun Yat-sen University at 3 sites in China.

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 22 inclusion and 37 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: status not confirmed, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: 2 years). 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 NCT04085250, which also lists 20 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 23 Apr 2024.

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