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

NCT04085250 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2019-FXY-119
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Stage III Non-small-cell Lung Cancer

Keywords

Stage III Non-Small Cell Lung Cancer; Neoadjuvant Chemotherapy plus nivolumab; Chemoradiotherapy; Nivolumab consolidation

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

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

  2 years

Secondary Outcomes (6)

• Overall Survival(OS)

  2 years

• Objective Response Rate(ORR)

  2 years

• Adverse Event

  2 years

• Symptoms and Health-related Quality of Life

  2 years

• Progression-free Survival

  2 years

Study Arms (2)

Nivolumab Consolidation

EXPERIMENTAL

Patients in experimental group will receive Nivolumab consolidation (360 mg) via iv infusion Q3W±3 days after the neoadjuvant therapy and concurrent chemo-radiotherapy.

Other: Neoadjuvant therapy; Other: Chemotherapy concurrent with radiotherapy; Radiation: Radiotherapy; Drug: Nivolumab

Observation

ACTIVE COMPARATOR

Patients in this group will receive observation after the neoadjuvant therapy and concurrent chemo-radiotherapy.

Other: Neoadjuvant therapy; Other: Chemotherapy concurrent with radiotherapy; Radiation: Radiotherapy; Other: Observation

Interventions

Neoadjuvant therapy OTHER

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.

Nivolumab Consolidation; Observation

Chemotherapy concurrent with radiotherapy OTHER

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

Nivolumab Consolidation; Observation

Radiotherapy RADIATION

Hypofractionated radiation technique was used to deliver a definitive radiation dose

Nivolumab Consolidation; Observation

Nivolumab DRUG

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.

Nivolumab Consolidation

Observation OTHER

Observation after the neoadjuvant therapy and concurrent chemo-radiotherapy.

Observation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

The First People's Hospital of Foshan

Foshan, Guangdong, 528000, China

Location

Sun yat-sen university cancer center

Guangzhou, Guangdong, 510000, China

Location

The first affliated hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510000, China

Location

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Neoadjuvant Therapy; Radiotherapy; Nivolumab; Observation

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)

Combined Modality Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Methods; Investigative Techniques

Study Officials

• Li Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Hui Liu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 11, 2019
• Study Start: November 28, 2019
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)