DUMAS: Neo-Adjuvant Immunotherapy for Pancoast Tumors

Trial Title: DUMAS: Neo-Adjuvant Immunotherapy for Pancoast Tumors

NCT ID: NCT05684276

Condition: NSCLC
Pancoast Tumor

Conditions: Official terms:
Pancoast Syndrome
Paclitaxel
Carboplatin
Nivolumab

Conditions: Keywords:
Neoadjuvant Treatment
Nivolumab

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Carboplatin
Description: Structure: The cis-diamino (cyclobutane-1, 1 dicarboxylate) plating. Stability: 24 hours at ambient temperature in 5% glucose, sodium chloride and glucose 5% solution solution or physiologic saline. It is recommended not to dilute with chlorinated solutions for this could affect the carboplatin. Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of ech center.
Arm group label: Experimental: Neodjuvant treatment + Adjuvant maintenance treatment

Other name: Paraplatin

Intervention type: Drug
Intervention name: Paclitaxel
Description: Structure: A diterpene whose composition is: 5b, 20-epoxy-1, 2a, 4,7b, 10b, 13a-hexa-hydroxy-11-en 9 one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)- N-benzoyl-3-phenylisoserine. Stability: Concentrations of 0.3-1.2 mg/ml in 5% dextrose or normal saline have demonstrated chemical and physical stability for more that 27 hours at ambient temperature (25ºC approximately). The intact vial must be stored between 15º and 25ºC. Guidelines on Paclitaxel administration: Paclitaxel must be administered by infusion over 3 hours in dextrose (D5W) or normal saline (NS). The concentration must not exceed 1.2 mg/ml.
Arm group label: Experimental: Neodjuvant treatment + Adjuvant maintenance treatment

Other name: Taxol

Intervention type: Drug
Intervention name: Nivolumab
Description: Structure: Nivolumab is a soluble protein consisting of 4 polypeptide chains. Route of administration: Intravenous infusion. Product Description: Nivolumab (BMS-936558-01) Injection drug product is a sterile, non-pyrogenic, single-use, isotonic aqueous solution formulated in 10 mg/ml. Storage Conditions: It must be stored at 2 to 8 degrees Cº and protected from light and freezing. Guidelines: The administration of nivolumab infusion must be completed within 24 hours of preparation.The dose of Nivolumab for the adjuvant treatment is 360 mg administered as an intravenous infusion over 30 minutes every 3 weeks (+/-3 days) for 3 cycles. For the maintenance adjuvant treatment the dose is nivolumab 480 mg Q4W (+/-3 days) over 30 minutes for 6 months (6 cycles). Subjects should be carefully monitored during nivolumab administration to follow infusion reactions. Doses of nivolumab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.
Arm group label: Experimental: Neodjuvant treatment + Adjuvant maintenance treatment

Other name: Opdivo

Summary: The goal of this clinical trial is to test the efficacy of induction treatment of immunotherapy and chemotherapy depending on the resection status for the treatment of non small cell lung cancer patients diagnosed with pancoast tumor. The main objectives it aims to answer are: - Complete resection rate after induction treatment with chemotherapy plus nivolumab - Overall Survival and Progression Free Survival at 24 months The sample size is 40 patients.

Detailed description: This is an open-label, phase II, single-arm, multi-centre clinical trial. The total sample size is 40 patients. The population to be included are previously untreated patients with histologically- or cytologically- documented NSCLC diagnosed with Pancoast tumor. Patients will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC6 for 3 cycles every 21 days (+/- 3 days) as neoadjuvant treatment followed by surgery and 6 months of adjuvant treatment with Nivolumab 480 mg Q4W (+/- 3 days) if applicable and depending on surgery results. Patients that will not receive adjuvant treatment will start follow up phase after end of treatment visit. Follow up for all patients must be done for 2 years. The primary objective is to evaluate the complete resection (R0) rate after induction treatment defined as the absence of residual tumor in patients treated with neoadjuvant chemo-immunotherapy.Secondary objectives and endpoint are Overall survival rate at 24 months and disease-free survival rate at 24 months. Patient accrual is expected to be completed within 2 years excluding a run-in-period of 3 months. Treatment and follow-up are expected to extend the study duration to a total of 5 years. The study will end once survival follow-up has concluded.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 1. Previously untreated patients with histologically- or cytologically- documented NSCLC diagnosed with Pancoast tumor according to 8th edition of the TNM (stages IIB, IIIA and T3N2 (IIIB) patients) - 2. PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before enrollment) to rule out the presence of distant disease. Also, a brain CT-SCAN or brain MRI will be done at baseline - 3. Positive mediastinal lymph nodes by PET-CT must be confirmed histologically. Mediastinal involvement may be considered without the need for histological confirmation when there is a mass of lymph nodes in which the margins cannot be distinguished - 4. Measurable or evaluable disease (according to RECIST 1.1 criteria) - 5. ECOG (Performance status) 0-2 - 6. Patients with a life expectancy of at least more than 12 weeks - 7. Patients aged > 18 years and ≤ 75 years - 8 Screening laboratory values must meet the study criteria and should be obtained within 14 days prior to enrollment - 9. Correct lung function without bronchodilators, defined by forced expiratory volume in 1 second (FEV1) >40% of the predicted normal volume, and a pulmonary diffusing capacity for carbon monoxide (DLCO) >40% of the predicted normal value - 10. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention - 11. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before enrollment. - 12. All sexually active men and women of childbearing potential must use an effective contraceptive method during the study treatment and for a period of at least 12 months following the last administration of trial drugs - 13. Patient capable of proper therapeutic compliance and accessible for correct follow-up. Exclusion Criteria: - 1. Patients that receive previous treatment with antineoplastic drugs, chest radiotherapy, or previous surgery for lung cancer or for another reason - 2. Pleural or pericardial effusion: Both will be considered indicative of metastatic disease unless proven otherwise. Those that, even being cytologically negative for malignancy, are exudates, will also be excluded. Patients with pleural effusion not visible on chest X-ray or too small to perform diagnostic puncture safely may be included. - 3. Patients with a weight loss >10% in the 3 months prior to the study entry - 4. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene or ROS1 mutations. - 5. Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included. - 6. Patients with symptomatic neuropathy > grade 1 according to the CTCAE v5.0 and that were not related to the tumor - 7. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. - 8. Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team. - 9. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anticancer therapy - 10. Patients with uncontrolled comorbidities that may affect the clinical trial compliance - 11. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required during the study period. - 12. Any medical, mental, neurological or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information sheet. - 13. Patients in any psychological, familiar, sociological or geographical situation that may hinder compliance with the study protocol and/or the follow up - 14. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways - 15. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection - 16. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). - 17. Patients with know hypersensitivity to drugs with a structure similar to the study drug and/or history of allergy to study drug components excipients - 18. Women who are pregnant or in the period of breastfeeding - 19. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Hospital De Mataro

Address:
City: Mataró
Zip: 08304
Country: Spain

Status: Recruiting

Contact:
Last name: Laura Puntí, MD

Investigator:
Last name: Laura Puntí, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Jerez De La Frontera

Address:
City: Jerez De La Frontera
Zip: 11407
Country: Spain

Status: Recruiting

Contact:
Last name: Mª Ángeles Moreno, MD

Investigator:
Last name: Mª Ángeles Moreno, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Puerta de Hierro

Address:
City: Majadahonda
Zip: 28222
Country: Spain

Status: Recruiting

Contact:
Last name: Mariano Provencio, MD

Investigator:
Last name: Mariano Provencio, MD
Email: Principal Investigator

Facility:
Name: Hospital General Universitario de Elche

Address:
City: Alicante
Zip: 03203
Country: Spain

Status: Recruiting

Contact:
Last name: María Guirado, MD

Investigator:
Last name: María Guirado, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitari Quiron Dexeus

Address:
City: Barcelona
Zip: 08028
Country: Spain

Status: Recruiting

Contact:
Last name: Andrés Aguilar, MD

Investigator:
Last name: Andrés Aguilar, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitari Vall d' Hebron

Address:
City: Barcelona
Zip: 08035
Country: Spain

Status: Recruiting

Contact:
Last name: Alex Martínez, MD

Investigator:
Last name: Alex Martínez, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínic De Barcelona

Address:
City: Barcelona
Zip: 08036
Country: Spain

Status: Not yet recruiting

Contact:
Last name: Noemí Reguart

Investigator:
Last name: Noemí Reguart, MD
Email: Principal Investigator

Facility:
Name: Hospital Parc Taulí

Address:
City: Barcelona
Zip: 08208
Country: Spain

Status: Recruiting

Contact:
Last name: Julia Giner, MD

Investigator:
Last name: Julia Giner, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario de Cruces

Address:
City: Bilbao
Zip: 48903
Country: Spain

Status: Recruiting

Contact:
Last name: Eider Azkona Uribelarrea, MD

Investigator:
Last name: Eider Azkona Uribelarrea, MD
Email: Principal Investigator

Facility:
Name: Hospital San Pedro De Alcántara

Address:
City: Cáceres
Zip: 10003
Country: Spain

Status: Recruiting

Contact:
Last name: Rubén Alonso Calderón, MD

Investigator:
Last name: Rubén Alonso Calderón, MD
Email: Principal Investigator

Facility:
Name: Hospital Josep Trueta

Address:
City: Girona
Zip: 17007
Country: Spain

Status: Recruiting

Contact:
Last name: Elia Sais Girona, MD

Investigator:
Last name: Elia Sais Girona, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario de Jaén

Address:
City: Jaén
Zip: 23007
Country: Spain

Status: Not yet recruiting

Contact:
Last name: Ana Laura Ortega Granados, MD

Investigator:
Last name: Ana Laura Ortega Granados, Md
Email: Principal Investigator

Facility:
Name: Hospital Universitario Lucus Augusti

Address:
City: Lugo
Zip: 27003
Country: Spain

Status: Recruiting

Contact:
Last name: Begoña Campos, MD

Investigator:
Last name: Begoña Campos, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico San Carlos

Address:
City: Madrid
Zip: 28040
Country: Spain

Status: Recruiting

Contact:
Last name: Carlos Aguado, MD

Investigator:
Last name: Carlos Aguado, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Fundación Jiménez Díaz

Address:
City: Madrid
Zip: 28040
Country: Spain

Status: Recruiting

Contact:
Last name: Manuel Dómine, MD

Investigator:
Last name: Manuel Dómine, MD
Email: Principal Investigator

Facility:
Name: Hospital 12 De Octubre

Address:
City: Madrid
Zip: 28041
Country: Spain

Status: Recruiting

Contact:
Last name: Luis Paz-Ares, MD

Investigator:
Last name: Luis Paz-Ares, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario la Paz

Address:
City: Madrid
Zip: 28046
Country: Spain

Status: Recruiting

Contact:
Last name: Javier De Castro, MD

Investigator:
Last name: Javier De Castro, MD
Email: Principal Investigator

Facility:
Name: Fundació Althaïa

Address:
City: Manresa
Zip: 08243
Country: Spain

Status: Recruiting

Contact:
Last name: Silvia Catot, MD

Investigator:
Last name: Silvia Catot, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Regional de Málaga

Address:
City: Málaga
Zip: 29010
Country: Spain

Status: Recruiting

Contact:
Last name: José Miguel Jurado, MD

Investigator:
Last name: José Miguel Jurado, MD
Email: Principal Investigator

Facility:
Name: Hospital Son Espases

Address:
City: Palma De Mallorca
Zip: 07120
Country: Spain

Status: Recruiting

Contact:
Last name: Raquel Marsé, MD

Investigator:
Last name: Raquel Marsé, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Salamanca

Address:
City: Salamanca
Zip: 37007
Country: Spain

Status: Recruiting

Contact:
Last name: Edel del Barco, MD

Investigator:
Last name: Edel del Barco, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Virgen Del Rocio

Address:
City: Sevilla
Zip: 41013
Country: Spain

Status: Recruiting

Contact:
Last name: Miriram Alonso, MD

Investigator:
Last name: Miriam Alonso, MD
Email: Principal Investigator

Facility:
Name: Consorci Sanitari de Terrassa

Address:
City: Terrassa
Zip: 08227
Country: Spain

Status: Recruiting

Contact:
Last name: Marc Campayo, MD

Investigator:
Last name: Marc Campayo, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico de Valencia

Address:
City: Valencia
Zip: 46010
Country: Spain

Status: Recruiting

Contact:
Last name: Amelia Insa, MD

Investigator:
Last name: Amelia Insa, MD
Email: Principal Investigator

Facility:
Name: Hospital General Universitario de Valencia

Address:
City: Valencia
Zip: 46014
Country: Spain

Status: Recruiting

Contact:
Last name: Ana Blasco, MD

Investigator:
Last name: Ana Blasco, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario Dr. Peset

Address:
City: Valencia
Zip: 46017
Country: Spain

Status: Recruiting

Contact:
Last name: Inmaculada Maestu, MD

Investigator:
Last name: Inmaculada Maestu, MD
Email: Principal Investigator

Facility:
Name: Hospital Universitario La Fe

Address:
City: Valencia
Zip: 46026
Country: Spain

Status: Not yet recruiting

Contact:
Last name: Francisco Aparisi, MD

Investigator:
Last name: Francisco Aparisi, MD
Email: Principal Investigator

Facility:
Name: Hospital Clínico Universitario de Valladolid

Address:
City: Valladolid
Zip: 47003
Country: Spain

Status: Recruiting

Contact:
Last name: Rafael López, MD

Investigator:
Last name: Rafael López, MD
Email: Principal Investigator

Facility:
Name: Complexo Hospitalario Universitario De Vigo

Address:
City: Vigo
Zip: 36204
Country: Spain

Status: Recruiting

Contact:
Last name: Joaquin Casal, MD

Investigator:
Last name: Joaquin Casal, MD
Email: Principal Investigator

Start date: May 12, 2023

Completion date: June 1, 2028

Lead sponsor:
Agency: Fundación GECP
Agency class: Other

Source: Fundación GECP

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05684276
http://www.gecp.org