Clinical Trials /

Neo-DIANA: Neoadjuvant Treatment for EGFR Mutated Patients

NCT04512430

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neo-DIANA: Neoadjuvant Treatment for EGFR Mutated Patients
  • Official Title: A Phase II Trial of Neoadjuvant Treatment Carboplatin-Pemetrexed-Bevacizumab Plus Atezolizumab for the Treatment of Locally Advanced and Potentially Resectable NSCLC Patients With EGFR Mutations

Clinical Trial IDs

  • ORG STUDY ID: GECP 20/01_Neo-DIANA
  • SECONDARY ID: 2020-000642-33
  • NCT ID: NCT04512430

Conditions

  • Non-Small Cell Lung Cancer, Positive for Epidermal Growth Factor Receptor Expression

Interventions

DrugSynonymsArms
AtezolizumabExperimental: Neo-Adjuvant Immunotherapy
BevacizumabExperimental: Neo-Adjuvant Immunotherapy
CarboplatinExperimental: Neo-Adjuvant Immunotherapy
PemetrexedExperimental: Neo-Adjuvant Immunotherapy

Purpose

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

Detailed Description

      This is an open-label, non-randomised, phase II, multi-centre clinical trial. Patients
      enrolled will receive Atezolizumab 1200mg + Bevacizumab 15mg/Kg + Carboplatin AUC6 +
      Pemetrexed 500mg/m2 for 3 cycles every 21 days (+/- 3 days) as neoadjuvant treatment followed
      by surgery and 6 months of adjuvant treatment with Atezolizumab 1200 mg Q4W (+/- 3 days).

      The primary objective is to evaluate the major pathologic response defined as 10 percent or
      fewer viable cancer cells detectable in the resected tumor and in lymph nodes in stage IIIA
      EGFR mutated patients treated in neoadjuvant setting with atezolizumab- bevacizumab-
      carboplatin and pemetrexed.

      Patient accrual is expected to be completed within 2 years excluding a run-in-period of 3-6
      months. Treatment and follow-up are expected to extend the study duration to a total of 6
      years. Patients will be followed 3 years after adjuvant treatment. The study will end once
      survival follow-up has concluded. This will be followed by a close out period of 4 months.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental: Neo-Adjuvant ImmunotherapyExperimentalNeoadjuvant 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).
  • Atezolizumab
  • Bevacizumab
  • Carboplatin
  • Pemetrexed

Eligibility 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). PET/CT
             including IV contrast (CT of diagnostic quality) will be performed at baseline (28
             days +10 before randomization).

          -  2. Tumor should be considered resectable before study entry by a multidisciplinary
             team

          -  3. Sensitizing EGFR mutation (Del Exon 19 and ins Exon 21).

          -  4. ECOG (Performance status) 0-1

          -  5. 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

          -  6. Measurable or evaluable disease according to RECIST v1.1.

          -  7. The patients need to have a forced expiratory volume (FEV1)≥ 1.2 liters or >40% p-
             predicted value.

          -  8. 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.

          -  9. Patients aged > 18 years.

          -  10. Patient capable of proper therapeutic compliance and accessible for correct
             follow-up.

          -  11. 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.

          -  12. 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.

          -  13. 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.

          -  14. 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

        Exclusion Criteria:

          -  1. All patients carrying other EGFR mutations.

          -  2. Patients with known anaplastic lymphoma kinase (ALK) fusion oncogene, STK11 ligand
             alteration or ROS1 translocations.

          -  3. Clinically significant comorbidities that impaired administration of platinum-based
             chemotherapy.

          -  4. 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.

          -  5. 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.

          -  6. Patients with other active malignancy requiring concurrent intervention and/or
             concurrent treatment with other investigational drugs or anti-cancer therapy.

          -  7. 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.

          -  8. 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.

          -  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. Active tuberculosis.

          -  12. 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.

          -  13. Patients with history of allergy to study drug components excipients.

          -  14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins.

          -  15. Women who are pregnant or in the period of breastfeeding.

          -  16. Sexually active men and women of childbearing potential who are not willing to use
             an effective contraceptive method during the study.

          -  17.

               -  Patients with active, known or suspected autoimmune disease, including but not
                  limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
                  erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular
                  thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis,
                  Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
                  glomerulonephritis.

               -  Patients with a history of autoimmune-related hypothyroidism on a stable dose of
                  thyroid replacement hormone are eligible for this study.

               -  Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin
                  regimen are eligible for this study.

               -  Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis would
                  be excluded) are permitted provided that they meet the following conditions:

                    -  Rash must cover less than 10% of body surface area (BSA).

                    -  Disease is well controlled at baseline and only requiring low-potency
                       topical steroids.

                    -  No acute exacerbations of underlying condition within the previous 12 months
                       (not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate,
                       retinoids, biologic agents, oral calcineurin inhibitors, high-potency or
                       oral steroids).

          -  18. Patients with any contraindication for bevacizumab administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response
Time Frame:From date of end of neoadjuvant treatment until the date of last follow up, assessed up to 36 months
Safety Issue:
Description:To evaluate the major pathologic response (MPR) defined as 10 percent or fewer viable cancer cells detectable in the resected tumor and in lymph nodes in stage IIIA EGFR mutated patients treated in neoadjuvant setting with atezolizumabbevacizumab- carboplatin and pemetrexed

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:To evaluate the Overall Survival (OS) rate at 1 year, 2 and 3 years
Safety Issue:
Description:defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
Measure:Progression-free survival
Time Frame:To evaluate at 1 year of treatment
Safety Issue:
Description:defined as the length of time from the date of diagnosis to the date of the first documented progression of disease
Measure:Complete response rate
Time Frame:From date of end of neoadjuvant treatment until the date of last follow up, assessed up to 36 months
Safety Issue:
Description:Rate of complete response: Disappearance of all target lesions. Lymph nodes selected as target lesions must each have reduction in the short axis to < 10 mm in order for the response to be considered complete. In this case, the sum of diameters may be > 0.Disappearance of all non-target lesions; lymph nodes selected as non-target lesions must be non-pathological in size (< 10 mm).
Measure:Downstaging after surgery
Time Frame:After surgery within the 4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment (day 42-49 after day 1 of cycle 3) (each cycle is 21 days +/- 3 days)
Safety Issue:
Description:To evaluate a reduction in the stage of a cancer
Measure:Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame:From the subject's written consent to participate in the study through 100 days after the final administration of the drug
Safety Issue:
Description:Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fundación GECP

Trial 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

Last Updated

August 12, 2020