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Trial record 2 of 96 for:    MPDL3280A

MPDL3280A-treatment-IST-UMCG

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by University Medical Center Groningen
Sponsor:
Information provided by (Responsible Party):
Prof.dr. E.G.E. de Vries, University Medical Center Groningen
ClinicalTrials.gov Identifier:
NCT02478099
First received: May 21, 2015
Last updated: September 13, 2016
Last verified: September 2016
  Purpose
To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial the investigators will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging.

Condition Intervention Phase
Bladder Cancer
Non Small Cell Lung Cancer
Breast Cancer
Drug: MPDL3280A
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MPDL3280A Treatment in Patients With Locally Advance or Metastatic Non-small Cell Lung, Bladder and Triple Negative Breast Cancer After Investigational Imaging

Resource links provided by NLM:


Further study details as provided by University Medical Center Groningen:

Primary Outcome Measures:
  • Evaluation of efficacy of MPDL3280A after investigational imaging as measured by objective response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate progression free survival (PFS) according to standard RECIST v1.1 as assessed by the investigator. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate duration of response (DOR) according to standard RECIST v1.1 as assessed by the investigator. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate DOR according to modified RECIST as assessed by the investigator. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate ORR according to modified RECIST as assessed by the investigator. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate PFS according to modified RECIST as assessed by the investigator. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the safety/tolerability (by analysis of adverse events) of MPDL3280A. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    Safety assessment through:

    • Incidence, nature and severity of adverse events, including protocol-defined events of special interest, graded according to NCI CTCAE4.0
    • Changes in laboratory test results, vital signs and physical findings.

  • To determine the number of patients with and patients without tumor tracer uptake with 89Zr-MPDL3280A and 18F-FB-IL2 (as assessed in the trials MPDL3280A-img-042015 and IL2-img-UMCG-2015), who also demonstrate response to MPDL3280A therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To correlate PD-L1 biopsy results as assessed in the trials MPDL3280A-img-042015 and IL2-img-UMCG-2015 to response to MPDL3280A therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the utility of biopsy at the time of apparent disease progression to distinguish apparent increases in tumor volume related to the immunomodulatory activity of MPDL3280A from true disease progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2016
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Treatment with MPDL3280A
Treatment with MPDL3280A
Drug: MPDL3280A
Anti-PD-L1 antibody

Detailed Description:

Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T cell responses against cancer can result in a significant survival benefit in patients with Stage IV cancer. PD-L1 is an extracellular protein that downregulates immune responses primarily in peripheral tissues through binding to its two receptors PD-1 and B7-1. Interruption of the PD L1/PD-1 pathway by the PD-L1 targeting antibody MPDL3280A, represents an attractive strategy to reinvigorate tumor-specific T cell immunity. For PD1/PD-L1 pathway inhibition PD-L1 tumor surface expression was proposed as a potential biomarker. In early clinical trials, PD-L1 expression has been associated with response to PD1/PD-L1 inhibition. However, other clinical trials reported response to PD1/PD-L1 checkpoint inhibitors in a big patient groups who were PD-L1-negative assessed by a single biopsy. Another obstacle to using PD-L1 expression as predictive biomarker might be its potential heterogeneous expression and fast dynamics PD-L1 tumor expression and whole body distribution, as well as baseline activation status of the immune system are being assessed in two investigational imaging trials MPDL3280A-img-042015 or IL2-img--UMCG-2015.

To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial we will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging. Acquired data could lead to improved, more patient friendly, more easily accessible and possibly less expensive procedures for patient selection. Subsequently, the efficacy of (combinations of) checkpoint inhibition could also be improved, thus preventing unnecessary toxicity and reducing health care costs.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically documented solid locally advanced or metastatic NSCLC, bladder cancer or TNBC.
  2. Participation within the 18F-IL2 imaging trial (IL2-img-UMCG-2015) or 89Zr-MPDL3280A antibody imaging trial (MPDL3280A-img-042015) before participation in the MPDL3280A treatment trial.
  3. Patient must have undergone a fresh tumor biopsy for PD-L1 assessment performed as part of one of the investigational imaging trials.
  4. Patients are eligible if disease progression during or following first-line chemotherapy or any subsequent treatment lines for locally advanced or metastatic NSCLC, TNBC or bladder cancer occurred.

    • Additional criteria for bladder cancer:

    oPatients with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy are eligible if ≤ 12 months have elapsed between the last treatment administration and the date of recurrence.

    •Additional criteria for NSCLC: oPatients with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation for NSCLC are eligible if ≤ 6 months have elapsed between the last treatment administration and the date of recurrence.

    oPatients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must also have experienced disease progression (during or after treatment) or intolerance to treatment with erlotinib, gefitinib, or another EGFR tyrosine kinase inhibitor (TKI).

    oPatients with a known Anaplastic Lymphoma Kinase (ALK) fusion oncogene must also have experienced disease progression (during or after treatment) or intolerance to treatment with crizotinib or another ALK inhibitor.

  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Life expectancy ≥12 weeks.
  7. Signed Informed Consent Form.
  8. Ability to comply with protocol.
  9. Age ≥18 years.
  10. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
  11. Adequate hematologic and end organ function, defined by the following laboratory results obtained within ≤28days prior to the first full dose of MPDL3280A:

    • ANC ≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
    • WBC counts >2500/μL
    • Lymphocyte count ≥500/μL
    • Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
    • Hemoglobin ≥9.0 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion.
    • AST, ALT, and alkaline phosphatase ≤ 2.5× the upper limit of normal (ULN), with the following exceptions:

    oPatients with documented liver metastases: AST and/or ALT ≤ 5 × ULN oPatients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN

    •Serum bilirubin ≤ 1.5 × ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled.

    • INR and aPTT ≤ 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
    • Creatinine clearance ≥ 30 mL/min
  12. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one 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 MPDL3280A.

Exclusion Criteria:

  1. Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within ≤21 days prior to the first full dose of MPDL3280A; the following exceptions are allowed:

    • Hormone-replacement therapy or oral contraceptives.
    • TKIs approved for treatment of NSCLC discontinued >7 days prior to the first full dose of MPDL3280A. The baseline scan must be obtained after discontinuation of prior TKIs.
  2. Treatment with any other investigational agent, other than the investigational tracer 18F-FB-IL2 or 89Zr-MPDL3280A, or participation in another clinical trial with therapeutic intent within 28 days prior to the first full dose of MPDL3280A.
  3. CNS disease, including treated brain metastases.
  4. Leptomeningeal disease.
  5. Uncontrolled tumor-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 enrollment. 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 loco-regional therapy if appropriate prior to enrollment.
  6. 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.
  7. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

    • Patients, who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
    • Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
  8. Malignancies other than NSCLC, bladder cancer or TNBC within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death 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 with curative intent, ductal carcinoma in situ treated surgically with curative intent).
  9. Pregnant and lactating women.
  10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  11. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of the MPDL3280A formulation.
  12. History of 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 may be eligible for this study.
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be 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 exacerbation 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)
  13. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

    •History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

  14. Serum albumin < 2.5 g/dL.
  15. Positive test for HIV.
  16. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.

    • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to Cycle 1, Day 1.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  17. Active tuberculosis.
  18. Severe infections within 4 weeks prior to the first full dose of MPDL3280A, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  19. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
  20. Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1.

    •Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.

  21. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.

    •Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.

  22. Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
  23. Prior allogeneic bone marrow transplantation or solid organ transplant.
  24. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1or anticipation that such a live attenuated vaccine will be required during the study.

    •Influenza vaccination should be given during influenza season only (example: approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza vaccine (e.g. FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.

  25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
  26. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti−PD-1, and anti−PD-L1 therapeutic antibodies.

    •Patients who have had prior anti−CTLA-4 treatment may be enrolled, provided the following requirements are met: oMinimum of 6 weeks from the last dose of anti−CTLA-4 oNo history of severe immune related adverse effects from anti−CTLA-4 (CTCAE Grade 3 and 4)

  27. Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first full dose of MPDL3280A.
  28. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor agents) within 2 weeks prior to Cycle 1, Day 1.

    • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g. a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the sponsor.
    • The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02478099

Contacts
Contact: Elisabeth de Vries, Professor +31503610770 e.g.e.de.vries@umcg.nl
Contact: Carolien Schroder, MD PhD +31503610770 c.p.schroder@umcg.nl

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: E. G.E. de Vries, MD, PhD    +31 50 3612821    e.g.e.de.vries@umcg.nl   
Principal Investigator: E. G.E. de Vries, MD, PhD         
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Principal Investigator: Elisabeth de Vries, Professor UMCG
  More Information

Responsible Party: Prof.dr. E.G.E. de Vries, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT02478099     History of Changes
Other Study ID Numbers: ML29755 
Study First Received: May 21, 2015
Last Updated: September 13, 2016
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Center Groningen:
MPDL3280A
bladder cancer
non small cell lung cancer
triple negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 06, 2016