This is a randomized, phase II, multi-centre clinical trial. Sample size: 68 patients (Experimental Arm (Durvalumab + chemotherapy + FMT capsules): 34 patients, Control Arm (Durvalumab + chemotherapy): 34 patients) Population: Patients with stage IIA, IIB, IIIA and IIIB (only T3N2) non-small cell lung cancer In the Experimental arm, patients will receive Fecal Microbiota Transplant. Once done, the patient will start neoadjuvant treatment with Durvalumab + Chemotherapy . In the Control arm, patients will receive neoadjuvant treatment with Durvalumab + Chemotherapy. After neoadjuvant/induction treatment every patient will be evaluated to decide if the patient is a candidate for surgery or not. Patients that are R0 after surgery will receive Adjuvant treatment with Durvalumab. The primary objective is to evaluate the pathological Complete Response (pCR) rate. The total trial duration will be 6.5 years approximately.
This is a randomized, phase II, multi-centre clinical trial stratified according to PDL1 status (≥50 % or \<50%), and Akkermansia positive vs negative. In the pre-treatment phase, donors will be selected for preparing the fecal microbiota transplant with their samples. After that, patient's candidate with stage IIA, IIB, IIIA and IIIB (only T3N2) non-small cell lung cancer to study will be randomized in two different arms. In the Experimental arm, after randomization, patients will receive treatment with Rifaximin. Once done, the patient will start neoadjuvant treatment with Durvalumab IV + Chemotherapy for several cycles. In the Control arm, after randomization patients will receive neoadjuvant treatment with Durvalumab IV + Chemotherapy for several cycles. After neoadjuvant/induction treatment every patient will be evaluated by a multidisciplinary team in each participant hospital to decide if the patient is a candidate for surgery or not. Patients that are R0 confirmed by surgical pathology evaluation after surgery will receive Adjuvant treatment with Durvalumab IV. Sample size: 68 patients (Experimental Arm (Durvalumab + chemotherapy + FMT capsules): 34 patients, Control Arm (Durvalumab + chemotherapy): 34 patients) The primary objective is to evaluate the pathological Complete Response (pCR) rate in the intention to treat population (ITT population) The total trial duration will be 6.5 years approximately.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
Patients who are going to be donors must have been treated with neoadjuvant chemoimmunotherapy as part of the NADIM studies and must have achieved a pathological complete response (pCR). Additionally, they must be free of disease and complications such as a second tumor or treatment-related toxicity. Samples must be collected from patients who achieved pCR after surgery. Patients in the Experimental Arm will receive an antibiotic treatment, followed by the administration of capsules as part of the fecal microbiota transplant (FMT).
Durvalumab is a human monoclonal antibody of the immunoglobulin G1 kappa (IgG1κ) subclass that inhibits binding of programmed cell death ligand (PD-L1). Durvalumab (MEDI4736) binds with high affinity and specificity to human PD-L1 and blocks its interaction with PD-1 and CD80. Pharmaceutical form: Concentrate for solution for infusion (sterile concentrate).Clear to opalescent, colorless to light yellow solution, with no visible particles. The solution has an approximate pH of 6.0 and an osmolality of approximately 400 mOsm/kg. Durvalumab will be administered as part of both the neoadjuvant and adjuvant phases of the study.
Neoadjuvant / induction treatment: Durvalumab Paclitaxel Carboplatin Neoadjuvant / induction treatment: 4 cycles will be administered prior to the assessment for surgery. Route of administration Paclitaxel: Intravenous infusion. Guidelines of Paclitaxel administration: Paclitaxel must be administered by infusion 200mg/m2 over 3 hours
Neoadjuvant / induction treatment: Durvalumab Paclitaxel Carboplatin\* \*Infusion at the end of the Paclitaxel infusion. Neoadjuvant / induction treatment 4 cycles will be administered prior to the assessment for surgery. Route of administration Carboplatin: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center.
Hospital General Universitario de Alicante
Alicante, Alicante, Spain
Hospital General Universitario De Elche
Elche, Alicante, Spain
ICO Badalona, Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitari Quiron Dexeus
Barcelona, Barcelona, Spain
Hospital Universitari Vall d' Hebron
Barcelona, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, Spain
ICO Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Clínico San Cecilio
Granada, Granada, Spain
Complexo Hospitalario Universitario De Santiago
Santiago de Compostela, La Coruña, Spain
Hospital Universitario Lucus Augusti
Lugo, Lugo, Spain
...and 10 more locations
Pathological Complete Response (pCR) rate
Pathological Complete Response (pCR) defined as the absence of residual tumor in lung and lymph nodes after surgery.
Time frame: From date of randomization until the date of last follow up, assessed up to 24 months
Progression free survival (PFS)
Progression free survival (PFS) defined as the time from initiation of treatment to the occurrence of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From date of randomization until the date of last follow up, assessed up to 24 months
Overall Survival (OS)
Overall survival (OS) defined as the time which begins at the start of treatment and up to the time of death or last follow up
Time frame: From date of randomization until the date of last follow up, assessed up to 24 months
Resectability rate (%)
Resectability rate defined as the percentage of patients resected divided by the total number of patients who received neoadjuvant treatment
Time frame: From date of randomization until the date of last follow up, assessed up to 24 months
Proportion of R0 resections (%)
Percentage of R0 resection will be calculated by dividing the total number of R0 resection patients by the total number of patients resected.
Time frame: From date of randomization until the date of last follow up, assessed up to 24 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.
Time frame: From the subject's written consent to participate in the study through 90 days after the final administration of the drug.]
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