Clinical Trials /

Atezolizumab Plus Bevacizumab in First Line NSCLC Patients

NCT03836066

Description:

This is a multi-center phase II clinical trial of atezolizumab in combination with bevacizumab as first line treatment for locally advanced or metastasic high-intermediate tumour mutation burden selected NSCLC patients. 102 patients will be enrolled in this trial to examine the efficacy of this combination measured by progression free survival according to response evaluation Criteria in solid tumours (RECIST) version 1.1.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab Plus Bevacizumab in First Line NSCLC Patients
  • Official Title: A Phase II Open Label Study of Atezolizumab in Combination With Bevacizumab as First Line Treatment for Locally Advanced or Metastasic High-intermediate Tumor Mutation Burden Selected Non-squamous Non-small Cell Lung Cancer (NSCLC) Patients.

Clinical Trial IDs

  • ORG STUDY ID: GECP 18/03_TELMA
  • NCT ID: NCT03836066

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Atezolizumab-BevacizumabTecentriq-AvastinExperimental: Atezolizumab plus Bevacizumab arm

Purpose

This is a multi-center phase II clinical trial of atezolizumab in combination with bevacizumab as first line treatment for locally advanced or metastasic high-intermediate tumour mutation burden selected NSCLC patients. 102 patients will be enrolled in this trial to examine the efficacy of this combination measured by progression free survival according to response evaluation Criteria in solid tumours (RECIST) version 1.1.

Detailed Description

      Chemotherapy-naïve patients high-intermediate TMB (TMB≥10 mutations/MB) and with locally
      advanced or metastatic non-squamous non-small cell lung cancer patients will be selected.
      Enroled patientswill receive 1200 mg of atezolizumab and 15mg/Kg of Avastin® (bevacizumab)
      administered by IV infusion every 21 days (+/- 3 days).

      The treatment will start within 1-5 days from enrolment. Atezolizumab may continue beyond
      disease progression per RECIST v1.1 until loss of clinical benefit, unacceptable toxicity,
      patient or physician decision to discontinue , or death. Bevacizumab will be administered
      until progression disease, unacceptable toxicity, patient or physician decision to
      discontinue or death.

      For all patients, tumour response data collection will continue until disease progression,
      even if the patient stops study treatment prior to disease progression.

      The primary endpoint is to evaluate the efficacy of Atezolizumab in combination with
      Bevacizumab as measured by Progression Free Survival according to RECIST Version 1.1.

      PFS after enrolment is defined as the time from enrolment to the first occurrence of disease
      progression or death from any cause, whichever occurs first.

      Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 46
      months. Treatment and follow-up are expected to extend the study duration to a total of 4.5
      years. Patients will be followed 1.5 years after the end of treatment independently of the
      cause of end of treatment. The study will end once survival follow-up has concluded.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental: Atezolizumab plus Bevacizumab armExperimental1 group, Atezolizumab 1200mb + Bevacizumab 15 mg/kg (IV),every 21 days.
  • Atezolizumab-Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female, aged ≥ 18 years old

          2. ECOG performance status of 0 or 1.

          3. Histologically or cytologically confirmed, Stage IIIB or IV non-squamous NSCLC
             according to 8th version of the International Association for the Study of Lung Cancer
             Staging Manual in Thoracic Oncology

          4. No prior treatment for Stage IIIB or IV non-squamous NSCLC.

          5. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or
             chemo-radiotherapy with curative intent for non-metastatic disease must have
             experienced a treatment-free interval of at least 6 months from randomization since
             the last chemotherapy, radiotherapy, or chemo-radiotherapy.

          6. Patients with a treated asymptomatic CNS metastasis are eligible, provided they meet
             all of the following criteria:

               1. Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
                  midbrain, pons, medulla or spinal cord).

               2. No ongoing requirement for corticosteroids as therapy for CNS disease.

               3. No stereotactic radiation within 7 days or whole-brain radiation within 14 days
                  prior to randomization.

               4. No evidence of interim progression between the completion of CNS-directed therapy
                  and the screening radiographic study. Patients with new asymptomatic CNS
                  metastases detected at the screening scan must receive radiation therapy and/or
                  surgery for CNS metastases. Following treatment, these patients may then be
                  eligible without the need for an additional brain scan prior to inclusion, if all
                  other criteria are met.

          7. Patients with high-intermediate Tumour Mutational Burden analysed by Foundation
             Medicine (≥10 mutations/ MB) performed by a Foundation Medicine laboratory on
             previously obtained archival tumour tissue or tissue obtained from a biopsy at
             prescreening (sample must fulfil minimal sample requirements of 20% tumour cellularity
             and a minimum surface of 25mm2).

          8. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only
             be considered as measurable disease if disease progression has been unequivocally
             documented at that site since radiation and the previously irradiated lesion is not
             the only site of disease.

          9. Adequate hematologic and organ function defined by the following laboratory results
             obtained within 14 days prior to randomization:

             Neutrophils ≥ 1500 cells/μL without granulocyte colony-stimulating factor support.

               -  Lymphocyte count ≥ 500/μL.

               -  Platelet count ≥ 100,000/μL without transfusion.

               -  Haemoglobin ≥ 9.0 g/dL. Patients may be transfused to meet this criterion.

               -  INR or aPTT ≤ 1.5 × upper limit of normal (ULN). This applies only to patients
                  who are not receiving therapeutic anticoagulation; patients receiving therapeutic
                  anticoagulation should be on a stable dose.

               -  AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions:
                  Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN. Patients
                  with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN.

               -  Serum bilirubin ≤ 1.25 × ULN. Patients with known Gilbert disease who have serum
                  bilirubin level ≤ 3 × ULN may be enrolled.

               -  Serum creatinine ≤ 1.5 × ULN or creatinine clearance of ≥45ml/min (based on the
                  Cockcroft Gault formula).

         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. 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 (oestrogen 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. Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR)
             gene.

          2. Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene.

          3. Patients with an STK-1 Ligand alteration.

          4. Patients with MDM2 amplification.

          5. Patients with ROS1 translocations.

          6. Active or untreated CNS metastases as determined by CT or magnetic resonance imaging
             (MRI) evaluation during screening and prior radiographic assessments.

          7. Spinal cord compression not definitively treated with surgery and/or radiation or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for > 2 weeks prior to randomization.

          8. Leptomeningeal disease.

          9. Uncontrolled tumour-related pain. Patients requiring pain medication must be on a
             stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy
             (e.g., bone metastases or metastases causing nerve impingement) should be treated
             prior to initiation of study drug. Patients should be recovered from the effects of
             radiation. There is no required minimum recovery period. Asymptomatic metastatic
             lesions whose further growth would likely cause functional deficits or intractable
             pain (e.g., epidural metastasis that is not currently associated with spinal cord
             compression) should be considered for locoregional therapy, if appropriate, prior to
             initiation of study drug.

         10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently). Patients with indwelling
             catheters (e.g., PleurX®) are allowed.

         11. Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12
             mg/dL or corrected serum calcium > ULN).

         12. Malignancies other than NSCLC within 5 years prior to randomization, with the
             exception of those with a negligible risk of metastasis or death (e.g., expected
             5-year OS > 90%) treated with expected curative outcome (such as adequately treated
             carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized
             prostate cancer treated surgically with curative intent, ductal carcinoma in situ
             treated surgically with curative intent).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy of Atezolizumab in combination with Bevacizumab
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 36 months
Safety Issue:
Description:To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival according to Response Evaluation Criteria in Solid Tumours (RECIST).

Details

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

Trial Keywords

  • NSCLC, Atezolizumab, Bevacizumab

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