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Atezolizumab Plus Bevacizumab in First Line NSCLC Patients (TELMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03836066
Recruitment Status : Recruiting
First Posted : February 11, 2019
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
Fundación GECP

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Atezolizumab-Bevacizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : October 15, 2020
Estimated Study Completion Date : October 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Atezolizumab plus Bevacizumab arm
1 group, Atezolizumab 1200mb + Bevacizumab 15 mg/kg (IV),every 21 days.
Drug: Atezolizumab-Bevacizumab
Atezoluzumab 1200 mg + Bevacizumab 15 mg / kg
Other Name: Tecentriq-Avastin




Primary Outcome Measures :
  1. 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 ]
    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).



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. 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).

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): NCT03836066


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

Locations
Show Show 25 study locations
Sponsors and Collaborators
Fundación GECP
Investigators
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Principal Investigator: Mariano Provencio, PhD Hospital Universitario Puerta de Hierro
Additional Information:
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Responsible Party: Fundación GECP
ClinicalTrials.gov Identifier: NCT03836066    
Other Study ID Numbers: GECP 18/03_TELMA
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: May 12, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación GECP:
NSCLC, Atezolizumab, Bevacizumab
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
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors