Non-small Cell Lung Cancer Stage IPhase 2NCT04271384
Stereotactic Ablative Radiotherapy With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer
A Phase 2 study testing nivolumab in people with Non-small Cell Lung Cancer Stage I, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
Trial summary
Stage 1 non-small cell lung cancer (NSCLC) carries up to 30% chance of relapse in 5 years. This a phase 2 study that aims to determine the pathological complete response of the combination of stereotactic ablative radiotherapy (SABR) plus nivolumab as neoadjuvant treatment in early-stage non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Stage I
- What is being tested?
- nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteBrazil
- Study dates
- 12 Feb 2020to 15 Nov 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-small cell lung carcinoma (NSCLC), with longest diameter measuring up to 4 cm, restricted to one pulmonary lobe, with no clinical lymph node involvement through PET-CT and/or invasive staging, when indicated (not mandatory in patients with cT1-T2a and no uptake in lymph nodes through PET-CT);
- No previous treatment;
- Lesion susceptible to treatment with SABR, based on imaging evaluation by radiation oncologist;
- Good clinical surgery conditions (lung function test with an appropriate forced expiratory volume in one second [FEV1] and predicted post-operative FEV1 of 30% or higher), and lesion resectability, based on evaluation by a thoracic surgery team;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 - Appendix C: Criteria for Performance Status evaluation.
- Aged ≥ 18 years old.
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- Absence of immunosuppressive diseases, or autoimmune diseases on active treatment or with systemic treatment within the last 2 years, or conditions requiring use of immunosuppressive agents, or on corticotherapy at dose > 10 mg of prednisone or equivalent;
- Agreement with having all biomarkers of the study analyzed, including fresh biopsy tumor tissue, if needed.
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for following completion of therapy for 5 months if female and 7 months if male. Female subjects of child- bearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Patients must have an appropriate organic function evaluation within 4 weeks before recruitment, evidenced by:
- Hemoglobin ≥ 9.0 g/dL
- Leucometry > 2,000/mm3
- Absolute neutrophil count ≥ 1,000/mm3
- Platelet count ≥ 100,000/mm3
- Creatinine clearance ≥ 30 mL/min.
- Total bilirubin < 3 x upper limit of normal (ULN), except for patients with known Gilbert's syndrome.
- Aspartate aminotransferase (AST) < 3,0 x ULN.
- Alanine aminotransferase (ALT) < 3,0 x ULN.
Who cannot join
- Patients with contraindication to surgical treatment due to lack of medical conditions or deterioration of clinical state.
- Patients with any known or suspected active autoimmune diseases. Patients with vitiligo, type 1 diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis with no need of systemic treatment, or other controlled conditions may be recruited.
- Patients with conditions requiring use of corticosteroids at doses > prednisone 10 mg/day (or equivalent) or use of other immunosuppressive medications within 28 days before anticipated start of study drug. Inhaled corticoids are permitted, if needed.
- Patients with any known active chronic liver condition.
- Patients with history of previous malignancy treatment with curative intention within the last 2 years, except for in situ skin basal cell carcinoma and squamous cell carcinoma, which will be allowed. Patients with other malignancies not meeting the previous criteria may be considered for recruitment if the disease in question does not represent a competitive cause for death or has a low potential of progressing to metastatic disease. Patients with these conditions may be recruited if approved after review by the principal investigator.
- Patients with known positivity for human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) or any test positive for hepatitis B or hepatitis C virus representing non-eradicated active acute or chronic disease.
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- Previous treatment with anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies, or any other specific antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways.
- Major surgery within 28 days before the first dose of the study drug.
- Exposure to previous thoracic radiation therapy before the first dose of the study drug.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
- Known pregnancy or refusal of appropriate contraception in females with child-bearing potential.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Stereotactic Ablative Radiotherapy in Combination With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer: a Phase 2 Study
Stage 1 non-small cell lung cancer (NSCLC) carries up to 30% chance of relapse in 5 years. This a phase 2 study that aims to determine the pathological complete response of the combination of stereotactic ablative radiotherapy (SABR) plus nivolumab as neoadjuvant treatment in early-stage non-small cell lung cancer. The patients will receive standard SABR + nivolumab at a dose of 360 mg every 21 days for 3 doses. The patient will undergo surgery 10 weeks after the last radiotherapy dose.
Read the detailed description
Stage 1 non-small cell lung cancer (NSCLC) carries up to 30% chance of relapse in 5 years. Surgery is standard-of-care for this population. For patients who are not candidate for surgery, stereotactic ablative radiotherapy (SABR) is standard, with good local control but locoregional and distant failure. The use of preoperative SABR leads to a pathological complete response rate (pCR) of 60%. Anti-PD-1 has the ability to provoke a pCR in around 20% of patients as a single agent. Moreover, it has synergic activity with radiotherapy.
This a phase 2 study that aims to determine the pathological complete response of the combination of stereotactic ablative radiotherapy plus nivolumab as neoadjuvant treatment in early-stage non-small cell lung cancer. The patients will receive standard SABR, given either as 3, 5 or 8 fractions (depending on tumor size and location) + nivolumab at a dose of 360 mg every 21 days for 3 doses. The patient will undergo surgery 10 weeks after the last radiotherapy dose. We will measure translational biomarkers associated with either pCR or resistance to therapy.
- Conditions
- Non-small Cell Lung Cancer Stage I
- Being tested
- nivolumab
- Keywords
- Non-small cell lung cancer, nivolumab, pd-1, radiotherapy, stereotactic body radiotherapy, radiosurgery, immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nivolumabCombination product
Also called stereotactic ablative radiotherapy
Combined neoadjuvant therapy consisting of nivolumab + SABR
| Study group | Role | What they receive |
|---|---|---|
| SABR + Nivolumab | Experimental | Pre-operative treatment with standard SABR (3 x 18 Gy or 5 x 10 Gy or 8 x 7.5 Gy) concomitant with nivolumab at 360 mg every 21 days x3 doses.
Standard-of-care surgery to be performed after 12 weeks from D1 of treatment. Receives: Combination Product: nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Pathologic complete response (pCR) after Pre-operative therapy
pCR is defined as absence of viable tumor cells after neoadjuvant therapy, evaluated on surgical specimen
Measured: 12 weeks after first day of neoadjuvant therapy
Secondary outcomes (9)
Major pathological response (MPR)
MPR will be defined as <10% of viable tumor cells
Measured: 12 weeks after first day of neoadjuvant therapy
Safety: Treatment-related adverse events with continuous toxicity measure as per CTCAE v4.0
Treatment safety will be evaluated as per CTCAE v4.0
Measured: Every 21 days during the 3 doses of nivolumab and during a 100-day period after the last dose of study-treatment
Objective response rate (ORR)
ORR will be evaluated as per RECIST v1.1
Measured: At 10 (+/- 2) weeks after treatment start.
Relapse-free survival (RFS) at 12 months
Relapse-free survival will be measured from the enrollment date until the date of radiological progression, unequivocal clinical progression or death.
Measured: 12-month rate
Overall survival (OS)
OS will be measured on the date of treatment D1 until date of death (regardless of cause)
Measured: 12-month rate
Resectability Rate
Rate of complete surgical resections after study treatment
Measured: From baseline to the day of surgery (12+-2 weeks)
30-day surgical mortality
Proportion of patients alive after 30 days from surgical resection
Measured: 30 days after surgery
Number of pathologic positive lymph nodes
Number of pathologic lymph nodes that were clinically negative and were found to be positive after surgery
Measured: From baseline to the day of surgery (12+-2 weeks)
Correlated translational endpoints
The following will be evaluated: mutation profile, transcriptome, immunohistochemical profile, and inflammatory infiltrate by flow cytometry from peripheral blood. Flow cytometry will be repeated for all patients in the surgical specimen and peripheral blood. The mutation profile, transcriptome and immunohistochemical profile will be repeated for patients who do not reach a pathological complete response in viable cells to evaluate for potential resistance mechanisms. The intestinal microbiome will be sequenced before and after treatment and correlated with the endpoints.
Measured: Baseline and at surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start12 Feb 2020
- Primary completion15 Nov 2023
- Study completion15 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer Stage IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gustavo Schvartsman, MD, PhD, Principal investigator, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04271384
- Sponsor's protocol ID
- NivoSABR
- Status last verified
- Dec 2023
- First submitted
- 10 Feb 2020
- Last updated
- 26 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic Ablative Radiotherapy in Combination With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer: a Phase 2 Study
- ClinicalTrials.gov ID
- NCT04271384
- Acronym / sponsor ID
- NivoSABR
- Conditions
- Non-small Cell Lung Cancer Stage I
- Keywords
- Non-small cell lung cancer, nivolumab, pd-1, radiotherapy, stereotactic body radiotherapy, radiosurgery, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Study start
- 12 Feb 2020 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stage 1 non-small cell lung cancer (NSCLC) carries up to 30% chance of relapse in 5 years. This a phase 2 study that aims to determine the pathological complete response of the combination of stereotactic ablative radiotherapy (SABR) plus nivolumab as neoadjuvant treatment in early-stage non-small cell lung cancer. The patients will receive standard SABR + nivolumab at a dose of 360 mg every 21 days for 3 doses. The patient will undergo surgery 10 weeks after the last radiotherapy dose.
Detailed description
Stage 1 non-small cell lung cancer (NSCLC) carries up to 30% chance of relapse in 5 years. Surgery is standard-of-care for this population. For patients who are not candidate for surgery, stereotactic ablative radiotherapy (SABR) is standard, with good local control but locoregional and distant failure. The use of preoperative SABR leads to a pathological complete response rate (pCR) of 60%. Anti-PD-1 has the ability to provoke a pCR in around 20% of patients as a single agent. Moreover, it has synergic activity with radiotherapy.
This a phase 2 study that aims to determine the pathological complete response of the combination of stereotactic ablative radiotherapy plus nivolumab as neoadjuvant treatment in early-stage non-small cell lung cancer. The patients will receive standard SABR, given either as 3, 5 or 8 fractions (depending on tumor size and location) + nivolumab at a dose of 360 mg every 21 days for 3 doses. The patient will undergo surgery 10 weeks after the last radiotherapy dose. We will measure translational biomarkers associated with either pCR or resistance to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SABR + Nivolumab | Experimental | Combination Product: nivolumabPre-operative treatment with standard SABR (3 x 18 Gy or 5 x 10 Gy or 8 x 7.5 Gy) concomitant with nivolumab at 360 mg every 21 days x3 doses. Standard-of-care surgery to be performed after 12 weeks from D1 of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Non-small cell lung carcinoma (NSCLC), with longest diameter measuring up to 4 cm, restricted to one pulmonary lobe, with no clinical lymph node involvement through PET-CT and/or invasive staging, when indicated (not mandatory in patients with cT1-T2a and no uptake in lymph nodes through PET-CT);
- No previous treatment;
- Lesion susceptible to treatment with SABR, based on imaging evaluation by radiation oncologist;
- Good clinical surgery conditions (lung function test with an appropriate forced expiratory volume in one second [FEV1] and predicted post-operative FEV1 of 30% or higher), and lesion resectability, based on evaluation by a thoracic surgery team;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 - Appendix C: Criteria for Performance Status evaluation.
Key exclusion criteria (12 listed)
- Patients with contraindication to surgical treatment due to lack of medical conditions or deterioration of clinical state.
- Patients with any known or suspected active autoimmune diseases. Patients with vitiligo, type 1 diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis with no need of systemic treatment, or other controlled conditions may be recruited.
- Patients with conditions requiring use of corticosteroids at doses > prednisone 10 mg/day (or equivalent) or use of other immunosuppressive medications within 28 days before anticipated start of study drug. Inhaled corticoids are permitted, if needed.
- Patients with any known active chronic liver condition.
- Patients with history of previous malignancy treatment with curative intention within the last 2 years, except for in situ skin basal cell carcinoma and squamous cell carcinoma, which will be allowed. Patients with other malignancies not meeting the previous criteria may be considered for recruitment if the disease in question does not represent a competitive cause for death or has a low potential of progressing to metastatic disease. Patients with these conditions may be recruited if approved after review by the principal investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nivolumabAlso: stereotactic ablative radiotherapyCombined neoadjuvant therapy consisting of nivolumab + SABR | Combination product | SABR + Nivolumab |
Primary outcome
Percentage of Pathologic complete response (pCR) after Pre-operative therapy
Time frame: 12 weeks after first day of neoadjuvant therapy
pCR is defined as absence of viable tumor cells after neoadjuvant therapy, evaluated on surgical specimen
9 secondary outcomes
Major pathological response (MPR)
Time frame: 12 weeks after first day of neoadjuvant therapy
Safety: Treatment-related adverse events with continuous toxicity measure as per CTCAE v4.0
Time frame: Every 21 days during the 3 doses of nivolumab and during a 100-day period after the last dose of study-treatment
Objective response rate (ORR)
Time frame: At 10 (+/- 2) weeks after treatment start.
Relapse-free survival (RFS) at 12 months
Time frame: 12-month rate
Overall survival (OS)
Time frame: 12-month rate
Resectability Rate
Time frame: From baseline to the day of surgery (12+-2 weeks)
30-day surgical mortality
Time frame: 30 days after surgery
Number of pathologic positive lymph nodes
Time frame: From baseline to the day of surgery (12+-2 weeks)
Correlated translational endpoints
Time frame: Baseline and at surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gustavo Schvartsman, MD, PhD principal investigator
Hospital Israelita Albert Einstein
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nivolumab in people with Non-small Cell Lung Cancer Stage I, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
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 18 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: finished, as of the sponsor's last update on 26 Dec 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 Brazil. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of Pathologic complete response (pCR) after Pre-operative therapy (time frame: 12 weeks after first day of neoadjuvant therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Dec 2023; AzTrials last refreshed its copy on 6 Nov 2026.