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Trial record 2 of 2 for:    agadir | ( Map: France )

Atezolizumab Combined With BDB001 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors (AGADIR)

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ClinicalTrials.gov Identifier: NCT03915678
Recruitment Status : Recruiting
First Posted : April 16, 2019
Last Update Posted : February 2, 2022
Sponsor:
Collaborators:
Roche Pharma AG
National Cancer Institute, France
Seven and Eight Biopharmaceuticals Inc
Information provided by (Responsible Party):
Institut Bergonié

Tracking Information
First Submitted Date  ICMJE April 8, 2019
First Posted Date  ICMJE April 16, 2019
Last Update Posted Date February 2, 2022
Actual Study Start Date  ICMJE March 31, 2021
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2020)
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with pancreatic cancer. [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with virus associated tumors. [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with non-small cell lung cancer. [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with soft-tissue sarcoma. [ Time Frame: 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of 6-month progression-free rat (PFR) and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed at 6 months following treatment onset and more than 24 weeks, based on RECIST 1.1 criteria.
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with bladder cancer. [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
  • Assessment of the antitumor activity of atezolizumab combined with BDB001 and radiotherapy in patients with triple negative breast cancer. [ Time Frame: Within 6 months of treatment onset ]
    Antitumor activity will be assessed in terms of disease control rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
Assessment of the antitumor activity of atezolizumab combined with G100 and radiotherapy (independently for each population). [ Time Frame: Within 6 months of treatment onset ]
Antitumor activity will be assessed in terms of objective response rate within 24 weeks of treatment onset and is defined as the proportion of patients with complete response (CR) or partial response (PR) observed within 24 weeks of treatment onset (while treated with the investigational product), based on RECIST 1.1 criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2020)
  • 6-month Progression-free rate (PFR) in patients with pancreatic cancer. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • 6-month Progression-free rate (PFR) in patients with virus-associated tumor. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • 6-month Progression-free rate (PFR) in patients with non-small cell lung cancer. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • 6-month Progression-free rate (PFR) in patients with bladder cancer. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • 6-month Progression-free rate (PFR) in patients with triple negative breast cancer. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • 6-month objective response rate (ORR) independently for each population. [ Time Frame: 6 months ]
    Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed at 6 months, based on RECIST 1.1 criteria.
  • Objective response rate (ORR) within 24 weeks of treatment onset, independently for each population. [ Time Frame: Within 6 months ]
    Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed within 24 wekks after treatment onset, based on RECIST 1.1 criteria.
  • Best overall response, independently for each population. [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determined once all the data for the patient is known (RECIST 1.1).
  • 1-year progression-free survival, independently for each population. [ Time Frame: 1 year ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.
  • 2-year progression-free survival, independently for each population. [ Time Frame: 2 years ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.
  • 1-year overall survival, independently for each population. [ Time Frame: 1 year ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).
  • 2-year overall survival, independently for each population. [ Time Frame: 2 years ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).
  • Safety profile, independently for each population: Common Terminology Criteria for Adverse Events version 5 [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
  • Tumor immune cells levels [ Time Frame: before treatment onset and cycle 3 day 1 (each cycle is 21 days) ]
    Levels of immune cells in tumor will be measured by immunohistochemistry.
  • Blood cytokines levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of cytokines in blood will be measured by ELISA.
  • Blood lymphocytes levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of lymphocytes in blood will be measured by flow cytometry.
  • Blood kynurenine levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of kynurenine in blood will be measured by ELISA.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • 6-month objective response (OR) independently for each population. [ Time Frame: 6 months ]
    Objective response is defined as the proportion of patients with complete response (CR) or partial response (PR) observed at 6 months, based on RECIST 1.1 criteria.
  • 6-month Progression-free rate (PFR), independently for each population. [ Time Frame: 6 months ]
    Progression-free rate is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST 1.1 criteria.
  • Best overall response, independently for each population. [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Best overall response is defined as the best response across all time points (RECIST 1.1). The best overall response is determined once all the data for the patient is known (RECIST 1.1).
  • 1-year progression-free survival, independently for each population. [ Time Frame: 1 year ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.
  • 2-year progression-free survival, independently for each population. [ Time Frame: 2 years ]
    Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST 1.1) or death (from any cause), whichever occurs first.
  • 1-year overall survival, independently for each population. [ Time Frame: 1 year ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).
  • 2-year overall survival, independently for each population. [ Time Frame: 2 years ]
    Overall survival is defined as the delay between the start date of treatment and the date of death (of any cause).
  • Safety profile, independently for each population: Common Terminology Criteria for Adverse Events version 5 [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
  • Tumor immune cells levels [ Time Frame: before treatment onset and cycle 3 day 1 (each cycle is 21 days) ]
    Levels of immune cells in tumor will be measured by immunohistochemistry.
  • Blood cytokines levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of cytokines in blood will be measured by ELISA.
  • Blood lymphocytes levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of lymphocytes in blood will be measured by flow cytometry.
  • Blood kynurenine levels [ Time Frame: baseline, cycle 1 day 1, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days) ]
    Levels of kynurenine in blood will be measured by ELISA.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Atezolizumab Combined With BDB001 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors
Official Title  ICMJE Atezolizumab Combined With BDB001 AnD Immunogenic Radiotherapy in Patients With Advanced Solid Tumors
Brief Summary Basket trial concept to independently and simultaneously assess the effects of the association of atezolizumab + BDB001 + radiotherapy in multiple solid tumors.
Detailed Description

6 independent, multicenter, prospective, single-arm phase II trials, based on 2-stage Simon's optimal design, will be conducted in parallel to assess the efficacy of atezolimab + BDB001+ radiotherapy, separately, in distinct populations of solid tumors:

  • Population 1: pancreatic cancer
  • Population 2: virus-associated tumors
  • Population 3: anti-PD-1/L1 refractory non-small lung cancer
  • Population 4: soft-tissue sarcoma
  • Population 5: anti-PD-1/L1 refractory bladder cancer
  • Population 6: triple negative breast cancer
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

6 independent single-arm, multicenter, phase II trials, based on 2-stage Simon's optimal design (Simon R, Controlled Clinical Trials 1989):

  • Population 1: pancreatic cancer
  • Population 2: virus-associated tumors
  • Population 3: non-small lung cancer
  • Population 4: soft-tissue sarcoma
  • Population 5: bladder cancer
  • Population 6: triple negative breast cancer
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor, Adult
  • Pancreatic Cancer
  • Virus-associated Tumors
  • Non Small Cell Lung Cancer
  • Melanoma
  • Bladder Cancer
  • Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: Association atezolizumab + BDB001 + RT

    A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

    BDB001 will be administered by a 30-minute intravenous infusion before atezolizumab, on Days 1, 8, and 15 of cycles 1, 2, and 3. Then from cycle 4 BDB001 will be administered on Day 1 every 3 weeks.

    Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration. All participants will be treated by high dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

  • Drug: Association atezolizumab + BDB001+ RT

    A treatment cycle consits of 3 weeks. Atezolizumab will be administered as a 1-hour infusion on day 1 every 3 weeks (1200 mg).

    BDB001 will be administered by a 30-minute intravenous infusion before atezolizumab, on Days 1, 8, and 15 of cycles 1, 2, and 3. Then from cycle 4 BDB001 will be administered on Day 1 every 3 weeks.

    Radiotherapy will start at least one week after the first administration of atezolizumab and at the latest before the 2nd administration. All participants will be treated by high dose irradiation in stereotactic conditions on non-injected metastasis: 3 to 5 fractions for a total dose between 27 Gy and 60 Gy.

Study Arms  ICMJE
  • Experimental: Population 1: Pancreatic cancer
    Participants with pancreatic cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001 + RT
  • Experimental: Population 2: Virus-associated tumors
    Participants with virus-associated tumors will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001+ RT
  • Experimental: Population 3: anti-PD-1/L1 refractory non-small lung cancer
    Participants with anti-PD-1/L1 refractory non-small lung cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001+ RT
  • Experimental: Population 4: Soft-tissue sarcoma
    Participants with soft-tissue sarcoma will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001 + RT
  • Experimental: Population 5: anti-PD-1/L1 refractory bladder cancer
    Participants with anti-PD-1/L1 refractory bladder cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001 + RT
  • Experimental: Population 6: Triple negative breast cancer
    Participants with triple negative breast cancer will be treated with Atezolizumab combined with BDB001 and radiotherapy.
    Intervention: Drug: Association atezolizumab + BDB001 + RT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2019)
247
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2025
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. histologically confirmed pancreatic cancer, virus-associated tumors [including papillomaviruses-related cancers (cervical, head and neck, and nasal), Epstein-Barr virus (nasopharyngeal carcinoma) and Kaposi's sarcoma-associated herpes virus), non-small cell lung cancer, soft-tissue sarcomas, bladder cancer, triple negative breast cancer. For population 4, diagnosis must be confirmed by the RRePS Network as recommended by the French NCI,
  2. Metastatic disease,
  3. Age ≥ 18 years,
  4. ECOG ≤ 1,
  5. At least two lesions: one lesion that can be treated by radiotherapy and one site of disease that must be uni-dimensionally ≥ 10 mm considered as measurable according to RECIST v1.1. This lesion will not be treated by radiotherapy, however, note that lesion(s) that will be treated by radiotherapy will also be considered as measurable. Note that the largest size of the metastases to be irradiated will be 3cm,
  6. Life expectancy > 6 months,
  7. At least one tumor site that can be biopsied for research purpose. Tumor lesion in close proximity to vascular structures such as large vessels, aneurysm or pulmonary arteriovenous malformation will not be considered for biopsy,
  8. Availability of archived paraffin-embedded tumor tissue for research purpose,
  9. Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
  10. Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements - population 3 and population 5 only

    • Have achieved a complete response, partial response or stable disease and subsequently had disease progression while still on anti-PD-1/L1 therapy
    • Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)
    • Have demonstrated disease progression as defined by RECIST v1.1 within 18 weeks from the last dose of the anti- PD-1/L1 therapy.
  11. Adequate hematological, renal, metabolic and hepatic functions
  12. No prior or concurrent malignant disease needing an active treatment,
  13. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
  14. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2,
  15. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion.
  16. Both women and men must agree to use an effective method of contraception throughout the treatment period and for five months after discontinuation of treatment.
  17. Voluntary signed and dated written informed consents prior to any specific study procedure,
  18. Participants with a social security in compliance with the French law.

Exclusion criteria:

  1. Previous treatment with a TLR agonist
  2. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
  3. Women who are pregnant or breast feeding,
  4. Participation in a study involving a medical or therapeutic intervention in the last 30 days,
  5. Known hypersensitivity to CHO cell products or to any involved study drug or of its formulation components,
  6. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
  7. Treatment with systemic immunosuppressive medications including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to inclusion.
  8. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before inclusion,
  9. Any of the following cardiac criteria: congestive heart failure ≥ New York Heart Association (NYHA) class 2, unstable angina, new-onset angina, myocardial infarction less than 6 months before inclusion, uncontrolled cardiac arrhythmias, known left ventricular ejection fraction (LVEF) <50%
  10. Individuals deprived of liberty or placed under legal guardianship,
  11. Prior organ transplantation, including allogeneic stem cell transplantation,
  12. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease,
  13. History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
  14. History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy.
  15. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  16. Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L).
  17. Severe infections within 2 weeks prior to inclusion, including but not limited to SARS-Cov-2 infection, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  18. Received therapeutic oral or IV antibiotics within 2 weeks prior to inclusion.
  19. Participant has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease is clinically stable at least 14 days prior to inclusion.
  20. Administration of a live, attenuated vaccine within 4 weeks before the start of study medication .
  21. Has known active hepatitis B or hepatitis C,known history of Human Immunodeficiency or known acquired immunodeficiency syndrome, known history of tuberculosis
  22. Patients with current retinal disorder confirmed by retinal examination (external ocular examination, routine slit lamp biomicroscopy of anterior ocular structures and evaluation of the anterior and posterior chamber,
  23. Patients who wear contact lenses unable to replace them with glasses.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antoine ITALIANO, MD, PhD +33 5.56.33.33.33 a.italiano@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD s.mathoulin@bordeaux.unicancer.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03915678
Other Study ID Numbers  ICMJE IB 2019-01
2019-000850-78 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Institut Bergonié
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institut Bergonié
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Roche Pharma AG
  • National Cancer Institute, France
  • Seven and Eight Biopharmaceuticals Inc
Investigators  ICMJE Not Provided
PRS Account Institut Bergonié
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP