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NADIM II: Neo-Adjuvant Immunotherapy (NADIMII)

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ClinicalTrials.gov Identifier: NCT03838159
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Fundación GECP

Brief Summary:

This is an open-label, randomised, two-arm, phase II, multi-centre clinical trial.

90 patients will be enrolled in this trial to examine the pathological Complete Response defined as the absence of residual tumor in lung and lymph nodes comparing patients treated with chemo-immunotherapy versus chemotherapy alone.


Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Paclitaxel Drug: Carboplatin Drug: Nivolumab Phase 2

Detailed Description:

This is an open-label, randomised, two-arm, phase II, multi-centre clinical trial. Patients randomised to the experimental arm will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 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). Patients randomized to the control arm will receive Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) followed by surgery.

The primary objective is pathological Complete Response (pCR) defined as the absence of residual tumor in lung and lymph nodes comparing patients treated with chemo-immunotherapy versus chemotherapy alone. Patient accrual is expected to be completed within 3 years excluding a run-in-period of 3 months. Treatment and follow-up are expected to extend the study duration to a total of 6.5 years. Patients will be followed 3 years after adjuvant treatment or surgery. The study will end once survival follow-up has concluded.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Neo-adjuvant Chemo/Immunotherapy Versus Chemotherapy Alone for the Treatment of Locally Advanced and Potentially Resectable Non-small Cell Lung Cancer (NSCLC) Patients.
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : March 15, 2022
Estimated Study Completion Date : March 15, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Neo-Adjuvant Immunotherapy
  • Neoadjuvant treatment (paclitaxel+carboplatin+nivolumab) will start within 1-3 days from enrollment/randomisation. 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)
  • Adjuvant treatment (Nivolumab): Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 3rd to 8th week (+ 7 days) from surgery and for 6 months.
Drug: Paclitaxel

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.

The infusions must be mixed as soon as possible before the start of each infusion since the stability of paclitaxel beyond 24 hours is not known.

In-line filtration is obligatory since a small number of fibers within the acceptable limits of the USP Particulate Matter Test for LVP have been reported. Cellulose acetate filters of 0.22-micron pore size (such as IVEX II) can be used. The solution that shows excessive particulate matter must be rejected.


Drug: Carboplatin
Carboplatin must be administered at the end of the Paclitaxel infusion

Drug: Nivolumab

Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains and 2 identical light chains.

The administration of nivolumab infusion must be completed within 24 hours of preparation.


Active Comparator: Control: Neo-Adjuvant chemotherapy
  • Neoadjuvant treatment (paclitaxel+carboplatin) will start within 1-3 days from enrollment/ randomisation. 3 cycleswill 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)
Drug: Paclitaxel

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.

The infusions must be mixed as soon as possible before the start of each infusion since the stability of paclitaxel beyond 24 hours is not known.

In-line filtration is obligatory since a small number of fibers within the acceptable limits of the USP Particulate Matter Test for LVP have been reported. Cellulose acetate filters of 0.22-micron pore size (such as IVEX II) can be used. The solution that shows excessive particulate matter must be rejected.


Drug: Carboplatin
Carboplatin must be administered at the end of the Paclitaxel infusion




Primary Outcome Measures :
  1. Evaluation of the pathological complete response (pCR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 45 months. ]
    The pathological complete response is defined as the absence of residual tumor in lung and lymph nodes in patients treated with chemo-immunotherapy versus patients treated with chemotherapy alone.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) and also, potentially resectable locally advanced NSCLC patients' stage IIIB with T3N2 disease according to 8th edition can be included. - PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline
  2. Tumor should be considered resectable before study entry by a multidisciplinary team
  3. ECOG (Performance status) 0-1
  4. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration/inclusion i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin > 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normal limits
  5. 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
  6. Patients aged > 18 years
  7. 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 beginning of chemotherapy.
  8. All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs
  9. Patient capable of proper therapeutic compliance and accessible for correct follow-up
  10. Measurable or evaluable disease (according to RECIST 1.1 criteria)

Exclusion Criteria:

  1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.
  2. 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.
  3. 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.
  4. 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.
  5. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy
  6. 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 2 years prior to study entry AND no additional therapy is required during the study period.
  7. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information
  8. 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 costimulation or immune checkpoint pathways
  9. 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
  10. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  11. Patients with history of allergy to study drug components excipients
  12. Women who are pregnant or in the period of breastfeeding
  13. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03838159


Contacts
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Contact: Eva Pereira +34934302006 epereira@gecp.org

Locations
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Spain
ICO Badalona Not yet recruiting
Badalona, Barcelona, Spain, 08916
Contact: Enric Carcereny, MD         
Principal Investigator: Enric Carcereny, MD         
ICO Hospitalet Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Contact: Ernest Nadal, MD         
Principal Investigator: Ernest Nadal, MD         
Hospital Universitario Insular de Gran canaria Not yet recruiting
Las Palmas De Gran Canaria, Gran Canaria, Spain, 35016
Contact: Delvys Rodríguez, MD         
Principal Investigator: Delvys Rodríguez, MD         
Complejo Hospitalario Universitario A Coruña Recruiting
A Coruña, La Coruña, Spain, 15006
Contact: Rosario García, MD-phD         
Principal Investigator: Rosario García         
Hospital Universitario Puerta de Hierro Not yet recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Virginia Calvo, MD         
Principal Investigator: Virginia Calvo, MD         
Complejo Hospitalario Universitario de Vigo Recruiting
Vigo, Pontevedra, Spain, 36036
Contact: Joaquín Casal, MD         
Principal Investigator: Joaquín Casal         
Hospital Universitario de Cruces Not yet recruiting
Baracaldo, Vizcaya, Spain, 48903
Contact: Guillermo López, MD         
Principal Investigator: Guillermo López, MD         
Hospital General de Alicante Recruiting
Alicante, Spain, 03010
Contact: Bartomeu Massutí, MD         
Principal Investigator: Bartomeu Massutí, MD         
Hospital Universitari Dexeus Not yet recruiting
Barcelona, Spain, 08028
Contact: Santiago Viteri, MD         
Principal Investigator: Santiago Viteri, MD         
Hospital Universitari Vall d' Hebron Not yet recruiting
Barcelona, Spain, 08035
Contact: Alex Martínez, MD         
Principal Investigator: Alex Martínez, MD         
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Noemí Reguart, MD         
Principal Investigator: Noemí Reguart, MD         
Hospital de Sant Pau Not yet recruiting
Barcelona, Spain, 08041
Contact: Margarita Majem, MD         
Principal Investigator: Margarita Majem         
Hospital Universitario Reina Sofía Not yet recruiting
Córdoba, Spain, 14004
Contact: Isidoro Barneto, MD         
Principal Investigator: Isidoro Barneto, MD         
Hospital Dr. Josep Trueta Recruiting
Girona, Spain, 17007
Contact: Joaquim Bosch, MD         
Principal Investigator: Joaquim Bosch         
Hospital Clínico San Carlos Not yet recruiting
Madrid, Spain, 28040
Contact: José Luis González, MD         
Principal Investigator: José Luis González, MD         
Hospital Universitario Fundación Jiménez Díaz Not yet recruiting
Madrid, Spain, 28040
Contact: Manuel Dómine, MD         
Principal Investigator: Manuel Dómine, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Santiago Ponce, MD         
Principal Investigator: Santiago Ponce, MD         
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Javier de Castro, MD         
Principal Investigator: Javier de Castro, MD         
Hospital General Universitario de Málaga Not yet recruiting
Málaga, Spain, 29010
Contact: Manuel Cobo, MD         
Principal Investigator: Manuel Cobo         
Hospital Clínico de Salamanca Not yet recruiting
Salamanca, Spain, 37007
Contact: Elvira del Barco, MD         
Principal Investigator: Elvira del Barco         
Hospital Virgen del Rocío Not yet recruiting
Sevilla, Spain, 41013
Contact: Reyes Bernabé, MD         
Principal Investigator: Reyes Bernabé         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Amelia Insa, MD         
Principal Investigator: Amelia Insa, MD         
Hospital General de Valencia Not yet recruiting
Valencia, Spain, 46014
Contact: Carlos Camps, MD         
Principal Investigator: Carlos Camps, MD         
Hospital Clínico Universitario de Valladolid Recruiting
Valladolid, Spain, 47003
Contact: Rafael López, MD         
Principal Investigator: Rafael López         
Hospital Clínico Lozano Blesa Not yet recruiting
Zaragoza, Spain, 50009
Contact: Dolores Isla, MD         
Principal Investigator: Dolores Isla         
Sponsors and Collaborators
Fundación GECP
Investigators
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Principal Investigator: Mariano Provencio, MD Hospital Puerta del Hierro

Additional Information:
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Responsible Party: Fundación GECP
ClinicalTrials.gov Identifier: NCT03838159     History of Changes
Other Study ID Numbers: GECP 18/02_NADIM II
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Nivolumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological