Stereotactic Ablative Radiotherapy With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer

NCT04271384 | Completed Phase 2

• 1 other identifier: NivoSABR
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Non-small Cell Lung Cancer Stage I

Keywords

Non-small cell lung cancer; nivolumab; pd-1; radiotherapy; stereotactic body radiotherapy; radiosurgery; immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  12 weeks after first day of neoadjuvant therapy

Secondary Outcomes (9)

• Major pathological response (MPR)

  12 weeks after first day of neoadjuvant therapy

• Safety: Treatment-related adverse events with continuous toxicity measure as per CTCAE v4.0

  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)

  At 10 (+/- 2) weeks after treatment start.

• Relapse-free survival (RFS) at 12 months

  12-month rate

• Overall survival (OS)

  12-month rate

Study Arms (1)

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.

Combination Product: nivolumab

Interventions

nivolumab COMBINATION_PRODUCT

Combined neoadjuvant therapy consisting of nivolumab + SABR

Also known as: stereotactic ablative radiotherapy

SABR + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead

Study Sites (1)

Hospital Israelita Albert Einstein

São Paulo, 05651-901, Brazil

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gustavo Schvartsman, MD, PhD

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: February 12, 2020
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)