Clinical trial NCT05684276: DUMAS: Neo-Adjuvant Immunotherapy for Pancoast Tumors
Official title: Phase II Clinical Trial of Neo-adjuvant Chemo/Immunotherapy Followed by Adjuvant Treatment Depending on the Resection Status for the Treatment of NSCLC Patients Diagnosed With Pancoast Tumor. A Multicenter Exploratory Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NSCLC
Pancoast Tumor
Keywords: Neoadjuvant Treatment
Nivolumab
Lead sponsor: Fundación GECP
Sponsor class: OTHER
First posted: 2023-01-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

Primary outcomes:
measure: Estimate progression-free survival (PFS)
timeFrame: From the date randomization until the date of last follow up, assessed up to 24 months
Secondary outcomes:
measure: Overall survival
timeFrame: From the date of randomization until the date of last follow up, assessed up to 24 months
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: From the subject's written consent to participate in the study through 100 days after the final administration of the drug
measure: Complete resection (R0) rate
timeFrame: From the date of completion of induction treatment until the date of last follow up, assessed up to 24 months
Other outcomes:
Locations:
city: Mataró
country: Spain
facility: Hospital De Mataro
state: Barcelona
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario Jerez De La Frontera
state: Cádiz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Elche
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic De Barcelona
city: Barcelona
country: Spain
facility: Hospital Parc Taulí
city: Bilbao
country: Spain
facility: Hospital Universitario de Cruces
city: Cáceres
country: Spain
facility: Hospital San Pedro De Alcántara
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Jaén
country: Spain
facility: Hospital Universitario de Jaén
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario la Paz
city: Manresa
country: Spain
facility: Fundació Althaïa
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Palma De Mallorca
country: Spain
facility: Hospital Son Espases
city: Salamanca
country: Spain
facility: Hospital Universitario Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Vigo
country: Spain
facility: Complexo Hospitalario Universitario De Vigo
Study officials:
affiliation: Fundación GECP President
name: Mariano Provencio, MD
role: STUDY_CHAIR
References: