Multimodality Treatment in Stage III Non-small Cell Lung Cancer (NSCLC)

• Register: ClinicalTrials.gov
• Last refreshed on: 29 January 2024
• Main ID: NCT04245514
• Date of registration: 16/01/2020
• Prospective Registration: Yes
• Primary sponsor: Swiss Group for Clinical Cancer Research
• Public title: Multimodality Treatment in Stage III Non-small Cell Lung Cancer (NSCLC)
• Scientific title: Immune-modulatory Radiotherapy to Enhance the Effects of Neoadjuvant PD-L1 Blockade After Neoadjuvant Chemotherapy in Patients With Resectable Stage III(N2) Non-small Cell Lung Cancer (NSCLC): A Multicenter Phase II Trial
• Date of first enrolment: July 15, 2020
• Target sample size: 90
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04245514
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Switzerland

Contacts

• Name: Sacha Rothschild, MD
• Affiliation: Universitätsspital Basel

• Name: Bernhard Scheibe, PhD

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent according to ICH-GCP regulations before registration and
prior to any trial specific procedures.

- Histologically (cytology is accepted if histology is not possible) confirmed NSCLC
(adeno-, squamous-, large cell carcinoma, or NSCLC not otherwise specified (NOS))
irrespective of genomic aberrations or PD-L1 expression status.

- Tumor stage T1-4>7 N2 M0 (i.e. T1-3 N2 or T4 N2 but T4 only allowed if due to size >
7cm, not allowed if due to invasion or nodule in different ipsilateral lobe),
according to the TNM classification, 8th edition, December 2016 (see Appendix 2).
Mediastinal lymph node staging has to follow the process chart.

- Tumor is considered resectable based on a multidisciplinary tumor board decision made
before neoadjuvant treatment. Resectable is when a complete resection can be achieved
according to Rami-Porta

- Patients with a prior malignancy (except NSCLC) and treated with curative intention
are eligible if all treatment of that malignancy was completed at least 2 years before
registration and the patient has no evidence of disease at registration. Less than 2
years is acceptable for malignancies with low risk of recurrence and/or no late
recurrence, after consultation with CI.

- Measurable disease per RECIST v1.1 criteria by PET/CT with contrast enhanced CT-scan.

- Tumor tissue is available for the mandatory translational research (formalin-fixed;
preferably histology, cytology allowed if histology is not possible)

- Age 18-75 years at time of registration

- WHO performance status 0-1

- Adequate bone marrow function: absolute neutrophil count = 1.5 x 109/L, platelet count
= 100 x 109/L, hemoglobin = 90 g/L (transfusion allowed)

- Adequate hepatic function: total bilirubin = 1.5 x ULN (except for patients with
Gilbert's disease = 3.0 x ULN), AST and ALT = 1.5 x ULN, AP = 2.5 x ULN.

- Adequate renal function: calculated creatinine clearance = 60 mL/min, according to the
formula of Cockcroft-Gault

- Appropriate lung function based on the ESTS guidelines:

- For pneumonectomy: FEV1 and DLCO =80%. If one of both <80%, an exercise test peak
VO2 >75% or 20ml/kg/min is needed

- For resection less than pneumonectomy (resection up to the calculated extent):
exercise test peak VO2 =35% or =10ml/kg/min, with predicted postoperative FEV1
and DLCO = 30%.

- NB: if Spiroergometry would be needed according to ESTS guidelines but is not
possible in due time due to patient factors or the center's resources alternative
assessment methods of fitness for resection can be used (e.g. Stair climbing
test, V/P scan)

- Adequate cardiac function according to investigator's decision based on evaluation of
risk according to NYHA classification

- Women of childbearing potential must use highly effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
until 90 days after the last dose of investigational drug. A negative pregnancy test
performed within 7 days before registration is required for all women of childbearing
potential.

- Men agree not to donate sperm or to father a child during trial treatment and until 90
days after the last dose of investigational drug.

Exclusion criteria:

- Presence of any distant metastasis or N3 disease. Brain metastases have to be excluded
by CT or MRI.

- Sulcus superior tumors (Pancoast tumors) or T4 for any other reason than size >7cm.

- Any previous treatment for NSCLC

- Any previous treatment with immune checkpoint inhibitors, including durvalumab

- Previous radiotherapy to the chest (with the exception of tangential breast
irradiation with minimal dose to lung and mediastinum, and superficial orthovoltage or
electron irradiation of localized skin lesions)

- Concomitant or recent (within 30 days of registration) treatment with any other
experimental drug and/or enrollment in another clinical trial.

- Concomitant use of other anti-cancer drugs or radiotherapy.

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV) unstable angina pectoris, history of myocardial infarction within the last three
months, serious arrhythmias requiring medication (with exception of atrial
fibrillation or paroxysmal supraventricular tachycardia), uncontrolled hypertension.

- Preexisting peripheral neuropathy (> Grade 1)

- Body weight less than 30 kg

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment.

- Known history of allogeneic organ transplant

- Active autoimmune disease or a syndrome requiring systemic treatment within the past 3
months or a documented history of clinically severe autoimmune disease. Exceptions:
vitiligo, resolved childhood asthma/atopy, hypothyroidism stable on hormone
replacement, Sjögren's syndrome

- Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,
ulcerative colitis)

- Concomitant or prior use of immunosuppressive medication within 28 days before
registration, with the exceptions of intranasal and inhaled corticosteroids, or
systemic corticosteroids which must not exceed 10 mg/day of prednisone or a dose
equivalent corticosteroid, and the premedication for chemotherapy

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information.

- Known hypersensitivity to trial drugs (cisplatin and docetaxel, durvalumab) or to any
excipient

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer

NSCLC

Intervention(s)

Radiation: Radiotherapy

Drug: Durvalumab

Primary Outcome(s)

Event-free survival (EFS) at 12 months [Time Frame: at 12 months]

Secondary Outcome(s)

Objective response (OR) after neoadjuvant chemotherapy [Time Frame: At the date of tumor assessment after neoadjuvant chemotherapy, estimated at approximately 9 weeks post-baseline]

Local Major pathological response (MPR) [Time Frame: At the date of tumor assessment after surgery, estimated at approximately 15 weeks post-baseline]

Event-free survival (EFS) [Time Frame: From the date of registration until the date of progressive disease, relapse, second tumor or death, whichever occurs first, assessed up to 20 years after registration]

Overall Major pathological response (oMPR) [Time Frame: At the date of tumor assessment after surgery, estimated at approximately 15 weeks post-baseline]

Pathological Complete Response (pCR) [Time Frame: At the date of tumor assessment after surgery, estimated at approximately 15 weeks post-baseline]

Overall survival (OS) [Time Frame: From the date of registration until the date of death from any cause, assessed up to 20 years after registration]

Nodal down-staging to < ypN2 [Time Frame: At the date of tumor assessment after surgery, estimated at approximately 15 weeks post-baseline]

Complete resection [Time Frame: At the date of tumor assessment after surgery, estimated at approximately 15 weeks post-baseline]

Recurrence-free survival (RFS) after R0 resection [Time Frame: From the date of surgery until the date of recurrence of loco-regional disease, appearance of metastases, or death, whichever occurs first, assessed up to 20 years after registration]

OR after neoadjuvant immuno-radiotherapy [Time Frame: At the date of tumor assessment after neoadjuvant immune-radiotherapy, estimated at approximately 13 weeks post-baseline]

Secondary ID(s)

SAKK 16/18

Source(s) of Monetary Support

Please refer to primary and secondary sponsors