Neo-DIANA: Neoadjuvant Treatment for EGFR Mutated Patients

NCT04512430 | Terminated Phase 2 Results

• 2 other identifiers: GECP 20/01_Neo-DIANA2020-000642-33
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 18

Brief Summary

This is an open-label, non-randomised, phase II, multi-centre clinical trial 26 patients will be enrolled in this trial to evaluate the major pathologic response in patients with neoadjuvant treatment with Carboplatin Pemetrexed Bevacizumab plus Atezolizumab in patients with non-small cell lung carcinoma locally advanced mutated in EGFR

Conditions

Non Small Cell Lung Cancer; EGFR Gene Mutation

Keywords

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Bronchial Neoplasms; Atezolizumab; Bevacizumab; Carboplatin; Pemetrexed; Neoadjuvant treatment; Adjuvant treatment; Antineoplastic Agents, Immunological; EGFR Mutation; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Response

  To determine the antitumor activity in terms of objective response rate (ORR) of neoadjuvant treatment with carboplatin-pemetrexed-bevacizumab plus atezolizumab for the treatment of locally advanced and potentially resectable NSCLC patients with EGFR mutations. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions.

  From date of end of neoadjuvant treatment until the date of last follow up, assessed up to 36 months

Study Arms (1)

Experimental: Neo-Adjuvant Immunotherapy

EXPERIMENTAL

* Neoadjuvant treatment: (Atezolizumab: 1200 mg, IV infusion+Bevacizumab: 15mg/Kg mg, IV infusion+Carboplatin: AUC6, IV infusion+Pemetrexed: 500 mg/m2, IV infusion) 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 4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment (day 42-49 after day 1 of cycle 3). * Adjuvant treatment: Atezolizumab: 1200 mg, IV infusion Q4W (+/- 3 days) for 6 months (6 cycles) 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 (6 cycles).

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Atezolizumab DRUG

Patients will receive 1200 mg of Atezolizumab every 21 days (QW3) (+/- 3 days) during neoadjuvant phase and every 28 days (QW4) (+/- 3 days) at adjuvant phase in a monitored setting where there is immediate access to trained personnel and adequate equipment/medicine to manage potentially serious reactions. First Infusion * No premedication administered for atezolizumab specifically is permitted * Infuse atezolizumab (1200 mg in a 250 mL 0.9% NaCl IV bag) over 60 (+/- 15) minutes. Subsequent Infusions: * If patient experienced infusion-related reaction during any previous infusion, premedication with antihistamines may be administered for Cycles \> 2 at the discretion of the treating physician. * If the patient tolerated the first infusion well without infusion-associated adverse events, the successive infusion may be delivered over 30 (+/- 10) minutes.

Also known as: Tecentriq

Experimental: Neo-Adjuvant Immunotherapy

Bevacizumab DRUG

Patients will receive 15mg/Kg of Avastin® (bevacizumab) administered by IV infusion every 21 days, for 3 cycles during neoadjuvant phase, in a monitored setting where there is immediate access to trained personnel and adequate equipment/medicine to manage potentially serious reactions.

Also known as: Avastin

Experimental: Neo-Adjuvant Immunotherapy

Carboplatin DRUG

Structure: The cis-diamino (cyclobutan-1, 1 dicarboxilate) platin. Stability: 24 hours at ambient temperature in 5% glucose, glucosaline or physiologic saline. It is recommended not to dilute with chlorinated solutions since this could affect the carboplatin. Route of administration: Intravenous infusion Patients will receive Carboplatin AUC6 administered by IV infusion every 21 days, for 3 cycles during neoadjuvant phase. Guidelines of Carboplatin administration: According to the standard of each center

Also known as: Paraplatin

Experimental: Neo-Adjuvant Immunotherapy

Pemetrexed DRUG

Patients will receive Pemetrexed 500mg/m2 administered by IV infusion every 21 days, for 3 cycles during neoadjuvant phase. Pemetrexed disodium (ALIMTA®, pemetrexed) is a novel pyrrolo\[2,3 d\]pyrimidine-based folic acid analogue. Route of administration: Intravenous infusion. Guidelines of Pemetrexed administration: According to the standard of each center

Also known as: Alimta

Experimental: Neo-Adjuvant Immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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). PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before randomization).
• \. Tumor should be considered resectable before study entry by a multidisciplinary team
• \. Sensitizing EGFR mutation (Del Exon 19 and ins Exon 21).
• \. ECOG (Performance status) 0-1
• \. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 ×109/L iii. Hemoglobin \> 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): a. Female CrCl = (140 - age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/dL b. Male CrCl = (140 - age in years) x weight in kg x 1.00/ 72 x serum creatinine in mg/dL 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. PT/APTT/INR within normal limits
• \. Measurable or evaluable disease according to RECIST v1.1.
• \. The patients need to have a forced expiratory volume (FEV1)≥ 1.2 liters or \>40% p- predicted value.
• \. 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.
• \. Patients aged \> 18 years.
• \. Patient capable of proper therapeutic compliance and accessible for correct follow-up.
• \. For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (\< 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of Atezolizumab and/or 6 months after the last dose of Bevacizumab, whichever is later. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD): intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
• \. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate \[\< 1% per year\] when used consistently and correctly, and to continue its use for 6 months after the last dose of Bevacizumab. Male patients should not donate sperm during this study and for at least 6 months after the last dose of Bevacizumab.
• \. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs. The same rules are valid for male patients involved in this clinical study if they have a partner of childbirth potential. Male patients must always use a condom.
• \. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

You may not qualify if:

• \. All patients carrying other EGFR mutations.
• \. Patients with known anaplastic lymphoma kinase (ALK) fusion oncogene, STK11 ligand alteration or ROS1 translocations.
• \. Clinically significant comorbidities that impaired administration of platinum-based chemotherapy.
• \. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• \. 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.
• \. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy.
• \. 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.
• \. 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.
• \. 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.
• \. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• \. Active tuberculosis.
• \. Severe infections within 4 weeks prior to be included in the study, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• \. Patients with history of allergy to study drug components excipients.
• \. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• \. Women who are pregnant or in the period of breastfeeding.

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (18)

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Insular de Gran canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Iruña, 31008, Spain

Location

Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36036, Spain

Location

Hospital Universitari Quiron Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, 08035, Spain

Location

ICO Girona, Hospital Josep Trueta

Girona, 17007, Spain

Location

Hospital Universitario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital General Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07120, Spain

Location

Hospital Clínico de Salamanca

Salamanca, 37007, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47003, Spain

Location

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Interventions

atezolizumab; Bevacizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

The recruitment was closed prematurely to due to slow recruitment, so there are no consistent data to achieve any relevant conclusion at this point.

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34934302006

Study Officials

• Mariano Provencio, MD

  Hospital Puerta del Hierro

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 13, 2020
• Study Start: December 2, 2020
• Primary Completion: July 19, 2024
• Study Completion: July 19, 2024
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (18)