Clinical trial • Phase II • Oncology|Respiratory

Durvalumab for Non-small cell lung cancer (stage III, N2) | Resectable locally advanced non-small cell lung cancer

Phase II trial of Durvalumab for Non-small cell lung cancer (stage III, N2) | Resectable locally advanced non-small cell lung cancer.

Overview

Trial Therapeutic Area
Oncology|Respiratory
Trial Disease
Non-small cell lung cancer (stage III, N2) | Resectable locally advanced non-small cell lung cancer
Trial Stage
Phase II
Drug Modality
Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
12-01-2024
First CTIS Authorization Date
17-04-2024

Trial design

Randomised, open-label, arms (radiotherapy regimens) per randomisation: a: 20x2 gy radiotherapy (weekdaily, 4 weeks); b: 5x5 gy radiotherapy (weekdaily, 1 week); c: 3x8 gy radiotherapy (on alternate days, 1 week). all subjects receive neoadjuvant chemotherapy (cisplatin/docetaxel or permitted alternatives) and peri-operative durvalumab; arms differ by radiotherapy regimen.-controlled Phase II trial across 1 site in Germany, Switzerland.

Randomised
Yes
Open Label
Yes
Comparator
Arms (radiotherapy regimens) per randomisation: A: 20x2 Gy radiotherapy (weekdaily, 4 weeks); B: 5x5 Gy radiotherapy (weekdaily, 1 week); C: 3x8 Gy radiotherapy (on alternate days, 1 week). All subjects receive neoadjuvant chemotherapy (cisplatin/docetaxel or permitted alternatives) and peri-operative durvalumab; arms differ by radiotherapy regimen.
Target Sample Size
80

Eligibility

Recruits 80 adults.

Inclusion criteria

  • {"criterion_text":"- 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\n- 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. Mediastinal lymph node staging has to follow the process chart.\n- Age 18-75 years at time of registration\n- WHO performance status 0-1\n- Adequate organ function (incl. eGFR ≥ 60 mL/min)"}

Exclusion criteria

  • {"criterion_text":"- Presence of any distant metastasis or N3 disease. Brain metastases have to be excluded by CT or MRI\n- Sulcus superior tumors (Pancoast tumors) or T4 for any other reason than size >7cm\n- Any previous treatment for NSCLC\n- Any previous treatment with immune checkpoint inhibitors, including durvalumab\n- 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)\n- Preexisting peripheral neuropathy (> Grade 1)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Event-free survival (EFS) at 12 months","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Event-free survival (EFS)\n- Recurrence-free survival (RFS) after R0 resection\n- Overall survival (OS)\n- Objective response (OR) after neoadjuvant chemotherapy\n- OR after neoadjuvant immunotherapy and immune-modulatory radiotherapy\n- Pathological complete response (pCR)\n- Local major pathological response (MPR)\n- Overall major pathological response (oMPR)\n- Rate of nodal down-staging to < ypN2\n- Complete resection rate\n- Pattern of recurrence (loco-regional, distant)\n- Adverse events (AEs) and surgical complications\n- Delay in surgery\n- Postoperative 30-day mortality","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
80
Recruitment Window Months
93
Consent Approach
Informed consent and screening. Adults (age 18-75) provide informed consent. No assent process or languages for consent specified.

Geography

Total Number Of Sites
1
Total Number Of Participants
80

Germany

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
15-08-2024
Processing Time Days
176
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Klinik für Radioonkologie
Principal Investigator Name
Cihan Gani
Principal Investigator Email
roinfo@med.uni-tuebingen.de
Contact Person Name
Cihan Gani
Contact Person Email
roinfo@med.uni-tuebingen.de
Number Of Participants
10

Switzerland

Number Of Sites
0

Sponsor

Primary sponsor

Full Name
Swiss Group for Clinical Cancer Research
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
CROLLL GmbH Auftragsforschungsinstitut (CRO)
Responsibilities
sponsorDuties codes: 1, 12

Third parties

  • {"country":"Switzerland","full_name":"Universitaetsspital Basel","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"CROLLL GmbH Auftragsforschungsinstitut (CRO)","duties_or_roles":"sponsorDuties codes: 1, 12","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Universitaetsspital Basel (Zlf, Hebelstrasse 20)","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
IMFINZI 50 mg/mL concentrate for solution for infusion.
Active Substance
Durvalumab
Modality
Monoclonal antibody
Routes Of Administration
CONCENTRATE FOR SOLUTION FOR INFUSION
Route
CONCENTRATE FOR SOLUTION FOR INFUSION
Authorisation Status
Authorised
Frequency
Adjuvant: 13 cycles of 28 days; Neoadjuvant durvalumab concurrent with radiotherapy (start corresponds to day 64 / week 10).
Maximum Dose
1500 mg (max daily); 21000 mg (max total)
Investigational Product Name
Doce onkovis 20 mg/ ml Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Docetaxel
Modality
Small molecule
Routes Of Administration
CONCENTRATE FOR SOLUTION FOR INFUSION
Route
CONCENTRATE FOR SOLUTION FOR INFUSION
Authorisation Status
Authorised
Frequency
Neoadjuvant chemotherapy: 3 cycles of 21 days (docetaxel part of cisplatin/docetaxel regimen); alternative chemo permitted if AEs.
Maximum Dose
85 mg/m2 (max daily); 255 mg/m2 (max total)
Investigational Product Name
Cisplatin Teva® 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Cisplatin
Modality
Small molecule
Routes Of Administration
CONCENTRATE FOR SOLUTION FOR INFUSION
Route
CONCENTRATE FOR SOLUTION FOR INFUSION
Authorisation Status
Authorised
Frequency
Neoadjuvant chemotherapy: 3 cycles of 21 days (cisplatin/docetaxel regimen)
Maximum Dose
100 mg/m2 (max daily); 300 mg/m2 (max total)
Investigational Product Name
Carboplat onkovis 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Carboplatin
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Frequency
Alternative to cisplatin if AEs in cycle 1 or 2 (carboplatin AUC 6 allowed)
Maximum Dose
400 mg/m2 (max daily); 800 mg/m2 (max total)
Investigational Product Name
Pemetrexed medac 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Pemetrexed
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Frequency
Permitted in cycle 2 and/or 3 as alternative if AEs require discontinuation of docetaxel (pemetrexed 500 mg/m2)
Maximum Dose
500 mg/m2 (max daily); 1000 mg/m2 (max total)
Investigational Product Name
Paclitaxel onkovis, 6 mg/ml, Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Paclitaxel
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Frequency
Permitted in cycle 2 and/or 3 as alternative if AEs require discontinuation of docetaxel (paclitaxel 200 mg/m2)
Maximum Dose
200 mg/m2 (max daily); 400 mg/m2 (max total)
Investigational Product Name
Vinorelbin onkovis 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Active Substance
Vinorelbine tartrate
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Frequency
Permitted in cycle 2 and/or 3 as alternative if AEs require discontinuation of docetaxel (vinorelbine 30 mg/m2)
Maximum Dose
30 mg/m2 (max daily); 120 mg/m2 (max total)
Combination Treatment
Yes

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