STUDY OF IMMUNE THERAPY (DURVALUMAB) BEFORE SURGERY IN EARLY STAGE NON SMALL CELL LUNG CANCER

• Register: EUCTR
• Last refreshed on: 6 February 2017
• Main ID: EUCTR2016-001849-15-FR
• Date of registration: 19/10/2016
• Prospective Registration: No
• Primary sponsor: IFCT
• Public title: STUDY OF IMMUNE THERAPY (DURVALUMAB) BEFORE SURGERY IN EARLY STAGE NON SMALL CELL LUNG CANCER
• Scientific title: A PHASE II PROSPECTIVE IMMUNE NEOADJUVANT THERAPY STUDY OF DURVALUMAB (MEDI4736) IN EARLY STAGE NON-SMALL CELL LUNG CANCER
• Date of first enrolment: 10/08/2016
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001849-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: Contact
• Affiliation: IFCT

• Name: Contact
• Affiliation: IFCT

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung.
- Tissue block of diagnosis must be available for submission after inclusion (one HES slide and one paraffin embedded block).
- Patients must be classified clinically as Stage IB (> 4cm in the longest diameter), II on the basis of clinical evaluation of 2009 TNM criteria. A pre-surgical PET scan of the thorax and a MRI or CT scan of the brain as well as thorax abdomen pelvis CT scan must be done prior to surgery and before inclusion. If preoperative CT and/or PET are suspicious for mediastinal nodal involvement, invasive mediastinal staging with mediastinoscopy or EBUS-TBNA must be performed. Station 5 or 6 lymph nodes may be accessed by anterior mediastinotomy or VATS.
- Pre-operative (neo-adjuvant) platinum based or other chemotherapy except the treatment of the protocol is not permissible. Pre-operative radiation therapy is not permissible
- The patient must have an ECOG performance status of 0, 1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion criteria:
- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
- A combination of small cell and non-small cell lung cancer or pulmonary carcinoid tumour.
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: patients with Grave’s disease and/or psoriasis not requiring systemic therapy within the last two years from inclusion are not excluded.
- History of primary immunodeficiency, history of allogenic organ transplant, use of immunosuppressive agents within 28 days of inclusion* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
* NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible.
- Live attenuated vaccination administered within 30 days prior to inclusion.
- History of hypersensitivity to durvalumab or any excipient.
- Mean QTc correction > 470msec using standard institutional method or history of familial long QT syndrome.
- Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF > 50% within 12 weeks prior to inclusion.
- Concurrent treatment with other investigational drugs or anti-cancer therapy.
- Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:
• known prior history of tuberculosis;
• known acute hepatitis B or C by serological evaluation;
• known Human immunodeficiency virus infection.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
- Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
- Known history of previous clinical diagnosis of tuberculosis


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stage IB (> 4 cm), II Non Small Cell Lung Cancer resectable
MedDRA version: 19.0 Level: PT Classification code 10029517 Term: Non-small cell lung cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0 Level: PT Classification code 10029518 Term: Non-small cell lung cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion

Primary Outcome(s)

Secondary Objective: - Tolerance, adverse effects and tolerability of durvalumab.
- Delay between start of treatment and surgery.
- Response Rate (RECIST 1.1).
- Metabolic response rate on TEP-FDG on pre-treatment PET-CT and pre-operative PET-CT after 3 durvalumab infusions, on both primary tumor and eventual nodes.
- Post-operative adverse events (AE).
- Pathological response (as assessed by microscopic histological examination, with at least one slide assessed by cm of tumor in the greatest diameter, i.e. 5 to 30 slides assessed). Major Pathological Response on surgical tissue (tumor + nodes) as centrally reviewed by a panel of IFCT Pathologists, on both tumor and resected nodes, and defined as semi-quantitative evaluation of less than 10% or remaining tumor cells, in surgical primary tumor and nodes samples.
- Disease Free Survival (DFS)
- Overall survival (OS)

Timepoint(s) of evaluation of this end point: After surgery

Main Objective: To assess the impact of neo-adjuvant therapy with durvalumab given by intravenous infusion for one month on the complete resection.

Primary end point(s): All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.
Margins are classified by the pathologist as:
R0 - no cancerous cells seen microscopically; this is the desired result
R1 - cancerous cells can be seen microscopically
R2 - even gross examination by the naked eye shows tumor tissue on the margin, indicating more remains on the patient.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - 4 weeks after surgery, 6 months and one year.
- Before surgery
- Before surgery
- Before surgery
- 4 weeks after surgery
- After surgery
- 6 months and one year after surgery then yearly
- 6 months and one year after surgery then yearly

Secondary end point(s): - Number of adverse effects and tolerability of durvalumab.
- Delay between start of treatment and surgery.
- Response Rate (RECIST 1.1).
- Metabolic response rate on TEP-FDG on pre-treatment PET-CT and pre-operative PET-CT after 3 durvalumab infusions, on both primary tumor and eventual nodes.
- Post-operative adverse events (AE).
- Pathological response (as assessed by microscopic histological examination, with at least one slide assessed by cm of tumor in the greatest diameter, i.e. 5 to 30 slides assessed). Major Pathological Response on surgical tissue (tumor + nodes) as centrally reviewed by a panel of IFCT Pathologists, on both tumor and resected nodes, and defined as semi-quantitative evaluation of less than 10% or remaining tumor cells, in surgical primary tumor and nodes samples.
- Disease Free Survival (DFS)
- Overall survival (OS)

Secondary ID(s)

IFCT-1601

Source(s) of Monetary Support

IFCT