DUMAS: Neo-Adjuvant Immunotherapy for Pancoast Tumors

Sponsor

Fundación GECP (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05684276

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
NSCLC Pancoast Tumor	Drug: Carboplatin Drug: Paclitaxel Drug: Nivolumab	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2028

Anticipated Study Completion Date :

Jun 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Neodjuvant treatment + Adjuvant maintenance treatment Neodjuvant treatment: Nivolumab: 360 mg intravenous Q3W Paclitaxel: 200mg/m2 infusion over 3 hours Carboplatin: AUC6 at the end of the Paclitaxel infusion Neoadjuvant treatment will start within 1-3 days from enrollment. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients must leave the study if there is evidence of progression. Patients with stable disease or partial response may be considered for surgery. Surgery: Surgery must be done within the 3rd-4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment (day 42-49 after day 1 of cycle 3) Depending on surgery results the patient will receive: Patients with degree of resection 'R0': Adjuvant treatment for 6 months with Nivolumab 480mg QW4 Patients with degree of resection 'R1' or 'R2': standard treatment according to local guidelines	Drug: Carboplatin 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. Other Names: Paraplatin Drug: Paclitaxel 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. Other Names: Taxol Drug: Nivolumab 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. Other Names: Opdivo

Arm

Intervention/Treatment

Experimental: Experimental: Neodjuvant treatment + Adjuvant maintenance treatment

Neodjuvant treatment: Nivolumab: 360 mg intravenous Q3W Paclitaxel: 200mg/m2 infusion over 3 hours Carboplatin: AUC6 at the end of the Paclitaxel infusion Neoadjuvant treatment will start within 1-3 days from enrollment. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients must leave the study if there is evidence of progression. Patients with stable disease or partial response may be considered for surgery. Surgery: Surgery must be done within the 3rd-4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment (day 42-49 after day 1 of cycle 3) Depending on surgery results the patient will receive: Patients with degree of resection 'R0': Adjuvant treatment for 6 months with Nivolumab 480mg QW4 Patients with degree of resection 'R1' or 'R2': standard treatment according to local guidelines

Drug: Carboplatin

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.

Other Names:

Paraplatin

Drug: Paclitaxel

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.

Other Names:

Taxol

Drug: Nivolumab

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.

Other Names:

Opdivo

Outcome Measures

Primary Outcome Measures

Complete resection (R0) rate [From the end of neoadjuvant treatment until end of surgery, assessed up to one month]
Evaluate the complete resection (R0) rate after induction treatment defined as the absence of residual tumor in patients treated with neoadjuvant chemo-immunotherapy

Secondary Outcome Measures

Overall survival [From the date of randomization until the date of last follow up, assessed up to 24 months]
Defined as the time between the date of randomization and the date of death
Disease-free survival rate [From the date of randomization until progression or date of last follow up, assessed up to 24 months]
Disease-free survival is defined as the length of time from enrollment to any of the following events: disease relapse, or death due to any cause. Disease relapse will have determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [From the subject's written consent to participate in the study through 100 days after the final administration of the drug]
It will be measured by the incidence of AE, SAE, immune-related AEs, deaths, and laboratory abnormalities. Adverse events will be graded according to CTCAE v5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)
1. 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
1. 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
1. Measurable or evaluable disease (according to RECIST 1.1 criteria)
1. ECOG (Performance status) 0-2
1. Patients with a life expectancy of at least more than 12 weeks
1. 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
1. 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
1. 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
1. 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.
1. 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
1. 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
1. 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.
1. Patients with a weight loss >10% in the 3 months prior to the study entry
1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene or ROS1 mutations.
1. 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.
1. Patients with symptomatic neuropathy > grade 1 according to the CTCAE v5.0 and that were not related to the tumor
1. 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.

1. 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.
1. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anticancer therapy
1. Patients with uncontrolled comorbidities that may affect the clinical trial compliance
1. 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.
1. 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.
1. Patients in any psychological, familiar, sociological or geographical situation that may hinder compliance with the study protocol and/or the follow up
1. 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
1. 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
1. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
1. Patients with know hypersensitivity to drugs with a structure similar to the study drug and/or history of allergy to study drug components excipients
1. Women who are pregnant or in the period of breastfeeding
1. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital De Mataro	Mataró	Barcelona	Spain	08304
2	Hospital Universitario Jerez De La Frontera	Jerez De La Frontera	Cádiz	Spain	11407
3	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
4	Hospital General Universitario de Elche	Alicante		Spain	03203
5	Hospital Universitari Quiron Dexeus	Barcelona		Spain	08028
6	Hospital Universitari Vall d' Hebron	Barcelona		Spain	08035
7	Hospital Clínic De Barcelona	Barcelona		Spain	08036
8	Hospital Parc Taulí	Barcelona		Spain	08208
9	Hospital Universitario de Cruces	Bilbao		Spain	48903
10	Hospital San Pedro De Alcántara	Cáceres		Spain	10003
11	Hospital Josep Trueta	Girona		Spain	17007
12	Hospital Universitario de Jaén	Jaén		Spain	23007
13	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
14	Hospital Clínico San Carlos	Madrid		Spain	28040
15	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
16	Hospital 12 De Octubre	Madrid		Spain	28041
17	Hospital Universitario la Paz	Madrid		Spain	28046
18	Fundació Althaïa	Manresa		Spain	08243
19	Hospital Universitario Regional de Málaga	Málaga		Spain	29010
20	Hospital Son Espases	Palma De Mallorca		Spain	07120
21	Hospital Universitario Salamanca	Salamanca		Spain	37007
22	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
23	Consorci Sanitari de Terrassa	Terrassa		Spain	08227
24	Hospital Clínico de Valencia	Valencia		Spain	46010
25	Hospital General Universitario de Valencia	Valencia		Spain	46014
26	Hospital Universitario Dr. Peset	Valencia		Spain	46017
27	Hospital Universitario La Fe	Valencia		Spain	46026
28	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003
29	Complexo Hospitalario Universitario De Vigo	Vigo		Spain	36204