NIvolumab COmbination With Standard First-line Chemotherapy and Radiotherapy in Locally Advanced Stage IIIA/B Non-Small Cell Lung Carcinoma

NCT02434081 | Completed Phase 2 Results DMC

• 3 other identifiers: ETOP 6-14 NICOLAS2014-005097-11SNCTP000001672
• Study Type: interventional
• Target: 94
• Locations: 5 countries
• Sites: 11

Brief Summary

The aim of the study is to investigate the tolerability (how severe the side effects are) and the efficacy (how well the treatment works) when nivolumab is added to the current standard treatment (chemotherapy and radiotherapy) given to patients with advanced NSCLC.

Conditions

Non-small Cell Lung Cancer Stage III

Keywords

NSCLC; IIIA/B

Outcome Measures

Primary Outcomes (1)

• Grade ≥3 Pneumonitis (CTCAE v4.0) up to 6 Months Post-radiotherapy

  It is defined as the number of patients reaching up to 6 months post-radiotherapy without any episode of CTCAE v4.0 grade ≥3 pneumonitis. It will be used as the primary endpoint for all patients followed for at least 6 months beyond radiotherapy.

  Time from enrolment until 6 months post-radiotherapy

Secondary Outcomes (5)

• Progression-free Survival by RECIST v1.1 (PFS)

  From the date of enrolment of the first patient up to 3 years, which is also 1 year after the enrolment of the last patient (i.e., from September 2016 to September 2019)

• (Grade ≥3) Pneumonitis-free Rate

  From the date of enrolment of the first patient up to 3 years, which is also 1 year after the enrolment of the last patient (i.e., from September 2016 to September 2019)

• Objective Response Rate (ORR)

  From the date of enrolment of the first patient up to 3 years, which is also 1 year after the enrolment of the last patient (i.e., from September 2016 to September 2019)

• Time to Treatment Failure (TTF).

  From the date of enrolment of the first patient up to 3 years, which is also 1 year after the enrolment of the last patient (i.e., from September 2016 to September 2019)

• Overall Survival (OS)

  From the date of enrolment of the first patient up to 4 years (i.e., from September 2016 to September 2020).

Study Arms (1)

Chemo-radiotherapy with concurrent nivolumab

EXPERIMENTAL

4 doses of nivolumab 360mg concurrently with standard chemo-radiotherapy, followed by 480mg for up to 1 year from start of nivolumab treatment.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab is a fully human monoclonal antibody that targets the programmed death-1 (PD-1) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.Binding of PD-1 to its ligands, 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Nivolumab inhibits the interaction of programmed cell death Protein 1 (PD-1)with its ligands, PD-L1 and PD-L2, resulting in enhanced T-cell proliferation.

Also known as: BMS-936558

Chemo-radiotherapy with concurrent nivolumab

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non small cell lung carcinoma
• Locally advanced stage IIIA or III B (T0-3 N2-3 or T4N0-3 M0) NSCLC, according to 7th TNM classification.
• Within 35 days before beginning of first platinum-based chemotherapy cycle:
• Nodal status N2 or N3 must to be proven (by biopsy, EBUS, mediastinoscopy or thoracoscopy) except for overt cT4 disease.
• Whole body FDG-PET, plus contrast enhanced CT of thorax / upper Abdomen (from top of thorax until adrenal glands, and full liver and kidney included) in addition to or in combination with PET.
• Brain MRI (preferred) or high-quality brain CT with intravenous contrast at the time of staging mandatory.
• Measurable disease (according to RECIST v1.1 criteria)
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Life expectancy \> 3 months
• Previous delivery of a maximum of one 3-weekly cycle of platinum-based chemotherapy
• All AEs from previous therapies (including the first chemotherapy cycle in the context of this trial) resolved to grade \<2 (except fatigue, alopecia, nausea, lack of appetite and peripheral neuropathy).
• Adequate haematological function:
• WBC ≥ 2000/μL
• haemoglobin ≥ 9 g/dL

You may not qualify if:

• Patient with mixed small-cell and non-small-cell histologic features
• Patient with pleural or pericardial effusions proven to be malignant
• Prior chemotherapy, radiotherapy or molecular targeted therapy for NSCLC (with the exception of one cycle of chemotherapy given prior to enrolment into this trial)
• Patients with an active, known or suspected autoimmune disease. Patients are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Patient who has had in the past 3 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast.
• Patient with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient's capacity to participate in the trial.
• Ongoing clinically serious infections requiring systemic antibiotic or antiviral, antimicrobial, antifungal therapy.
• Known or suspected hypersensitivity to nivolumab or any of its excipients
• History of severe hypersensitivity reaction to any monoclonal antibody
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial results.
• Established pathological diagnosis of underlying interstitial lung disease or pulmonary fibrosis
• Women who are pregnant or in the period of lactation
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial treatment and for a period of at least 7 months (male participants) and 5 months (female participants) following the last administration of nivolumab.
• Patients receiving any concurrent anticancer systemic therapy
• HIV, active Hepatitis B or Hepatitis C infection

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Bristol-Myers Squibb: collaborator
• Frontier Science Foundation, Hellas: collaborator

Study Sites (11)

University Hospital Leuven

Leuven, Belgium

Location

Thoracic Oncology Centre Munich

Munich, Germany

Location

VUMC

Amsterdam, Netherlands

Location

MAASTRO Clinic

Maastricht, 6229 ET, Netherlands

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Catalan Institute of Oncology

Barcelona, 08907, Spain

Location

Hospital Virgen de la Salud

Toledo, 45071, Spain

Location

HFR Fribourg- Hôpital cantonal

Fribourg, 1708, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Hirslanden Klinik Zürich

Zurich, 8032, Switzerland

Location

University Hospital Zürich

Zurich, Switzerland

Location

Related Publications (2)

• Salama JK, Vokes EE. New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer. J Clin Oncol. 2013 Mar 10;31(8):1029-38. doi: 10.1200/JCO.2012.44.5064. Epub 2013 Feb 11.

  PMID: 23401449 BACKGROUND

• Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Epub 2017 May 24.

  PMID: 28551359 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

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

Results Point of Contact

• Title: Heidi Roschitzki-Voser
• Organization: European Thoracic Oncology Platform (ETOP)

NICOLAS@etop-eu.org

+41 31 511 94 18

Study Officials

• Solange Peters, MD PhD

  University of Lausanne Hospitals

  STUDY CHAIR

• Dirk De Ruysscher, MD PhD

  Maastro Clinic, Maastricht, The Netherlands

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: May 5, 2015
• Study Start: November 25, 2015
• Primary Completion: February 29, 2020
• Study Completion: March 31, 2020
• Last Updated: August 24, 2022
• Results First Posted: October 25, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); NL (2); BE (1); DE (1); CH (4)