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A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1)

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ClinicalTrials.gov Identifier: NCT02588131
Recruitment Status : Unknown
Verified October 2015 by Italian Network for Tumor Biotherapy Foundation.
Recruitment status was:  Recruiting
First Posted : October 27, 2015
Last Update Posted : October 27, 2015
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Italian Network for Tumor Biotherapy Foundation

Study Description
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Brief Summary:
This phase 2, open-label, single arm study aims to evaluate the efficacy of tremelimumab in combination with the anti-PD-L1 MEDI4736 in patients with unresectable malignant mesothelioma subjects

Condition or disease Intervention/treatment Phase
Pleural Mesothelioma Peritoneal Mesothelioma Drug: tremelimumab plus MEDI4736 Phase 2

Detailed Description:
The prognosis of malignant mesothelioma (MM) patients remains dismal and effective treatment represents a high un-met medical need. Investigators have recently reported promising clinical activity of the anti-CTLA-4 mAb tremelimumab in pre-treated MM patients: disease control rate (DCR) was 31%, and survival rate at 1- and 2-years were 48.3% and 36.7%, respectively. These initial findings were corroborated by a second study in which, based on retrospective pharmacokinetic analyses, an intensified schedule of tremelimumab was utilized. Fifty-two % of patients achieved a DCR (median duration 10.9 months). These intriguing clinical results and the emerging efficacy of immunomodulatory mAb targeting the PD-1/PD-L1 axis in different tumor types, prompted us to design the NIBIT-MESO-1 study aimed to investigate the efficacy of tremelimumab combined with the anti-PD-L1 MEDI4736 in MM patients.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Phase II Clinical Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Monoclonal Antibody in Unresectable Malignant Mesothelioma Subjects: The NIBIT-MESO-1
Study Start Date : October 2015
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma
Drug Information available for: Durvalumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: tremelimumab plus MEDI4736
Tremelimumab in combination with MEDI4736
 Drug: tremelimumab plus MEDI4736
tremelimumab1 mg/kg i.v over 60 minutes plus MEDI 4736 20 mg/kg i.v every four weeks for 4 doses, then MEDI4736 20 mg/kg IV every four weeks for additional 9 doses.
Other Name: MEDI4736 (durvalumab)


Outcome Measures
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Primary Outcome Measures :
  1. immune-related (ir)- objective response rate (ORR) [ Time Frame: 60 weeks ]
    proportion of subjects with complete response [CR] or partial Response [PR]) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively.


Secondary Outcome Measures :
  1. Immune-related-Disease control rate (ir-DCR) [ Time Frame: 60 weeks ]
    proportion of subjects with ir-CR, ir-PR, ir-stable disease according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively

  2. Disease control rate (DCR) [ Time Frame: 60 weeks ]
    proportion of subjects with CR, PR, stable disease according to the modified-RECIST or RECIST 1.1 in pleural or peritoneal subjects, respectively

  3. Immune-related-progression-free-survival (PFS) [ Time Frame: 60 weeks ]
    ir-PFS per ir-modified-RECIST or ir-RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined as the time between the date of randomization and the date of progression or death

  4. progression-free-survival (PFS) [ Time Frame: 60 weeks ]
    PFS per modified-RECIST or RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined as the time between the date of randomization and the date of progression or death

  5. Overall survival (OS) [ Time Frame: 120 weeks ]
    Overall Survival (OS) is defined as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.

  6. Safety (adverse events) [ Time Frame: 120 weeks ]
    The safety endpoints include adverse events (AEs) and serious adverse events (SAEs). Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all subjects who received at least 1 dose of treatment. Toxicity will be registered according to the NCICTC v 4.0

  7. Immune-related-ORR based on PD-L1 tumor expression [ Time Frame: 60 weeks ]
    proportion of subjects with PD-L1 positive or negative tumor expression who achieved a complete response [CR] or partial Response [PR]) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively.

  8. Immune-related-Disease control rate based on PD-L1 tumor expression [ Time Frame: 60 weeks ]
    proportion of subjects with PD-L1 positive or negative tumor expression who achieved a CR, PR, stable disease according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively

  9. Immune-related-progression- free-survival based on PD-L1 tumor expression [ Time Frame: 60 weeks ]
    ir-PFS per ir-modified-RECIST or ir-RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined in subjects with PD-L1 positive or negative tumor expression as the time between the date of randomization and the date of progression or death

  10. Overall survival based on PD-L1 tumor expression [ Time Frame: 120 weeks ]
    Overall Survival (OS) is defined in subjects with PD-L1 positive or negative tumor expression as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.


Eligibility Criteria
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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:

  • Willing and able to give written informed consent.
  • Histologic diagnosis of malignant mesothelioma.
  • Subjects who have refused a first line platinum-based chemotherapy, or subjects in progression of disease after a maximum of one line of platinum-based therapy for advanced disease.
  • Disease not amenable to curative surgery.
  • Measurable disease, per modified Response Evaluation Criteria in Solid Tumor [RECIST] for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma).
  • Life expectancy ≥ 12 weeks.
  • ECOG performance status of 0 or 1
  • Normal laboratory tests
  • Negative screening tests for HIV, Hepatitis B, and Hepatitis C.
  • Availability of archival tumor tissue or feasibility to perform a new tumor biopsy at screening phase.
  • Men and women, of and over 18 years old. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 180 days after the last dose of investigational drug.

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study.
  • Participation in another clinical study with an investigational product during the last 6 weeks.
  • Any previous treatment with a CTLA4, PD-1 or PD-L1 inhibitor, including tremelimumab or MEDI4736.
  • History of another primary malignancy except for: malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
  • Receipt of the last dose of anti-cancer therapy ≤ 6 weeks prior to the first dose of study drug.
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms using Bazett's Correction.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of tremelimumab and MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Any unresolved toxicity (CTCAE grade >2) from previous anti-cancer therapy.
  • Any prior Grade >3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1. Active or prior documented autoimmune or inflammatory disorders
  • History of primary immunodeficiency or allogeneic organ transplant.
  • History of hypersensitivity to tremelimumab or MEDI4736 or any excipient.
  • Uncontrolled intercurrent illness including, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses
  • Known history of previous clinical diagnosis of tuberculosis.
  • History of leptomeningeal carcinomatosis.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving tremelimumab and MEDI4736.
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Subjects with uncontrolled seizures.
Contacts and Locations
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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): NCT02588131


Contacts
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Contact: Luana Calabro', MD, PhD +39-0577586116 l.calabro@ao-siena.toscana.it
Contact: Michele Maio, MD, PhD +39-0577586335 mmaiocro@gmail.com

Locations
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Italy
Medical Oncology and Immunotherapy Division, University Hospital of Siena Recruiting
Siena, Italy, 53100
Contact: Luana Calabro', MD, PhD    +39-0577586116    l.calabro@ao-siena.toscana.it   
Contact: Michele Maio, MD, PhD    +39- 0577586335    mmaiocro@gmail.com   
Sponsors and Collaborators
Italian Network for Tumor Biotherapy Foundation
AstraZeneca
Investigators
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Principal Investigator: Luana Calabro', MD, PhD Medical Oncology and Immunotherapy Division, Univeristy Hospital os Siena, Siena, Italy
More Information
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Additional Information:

Publications:
Antonia et al. A Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients with advanced non-small cell lung cancer (NSCLC). ASCO 2015 (Abstract #3014).

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Italian Network for Tumor Biotherapy Foundation
ClinicalTrials.gov Identifier: NCT02588131    
Other Study ID Numbers: NIBIT-MESO-1
First Posted: October 27, 2015    Key Record Dates
Last Update Posted: October 27, 2015
Last Verified: October 2015
Keywords provided by Italian Network for Tumor Biotherapy Foundation:
tremelimumab
anti-PD-L1 MEDI4736 (Durvalumab)
malignant mesothelioma
Additional relevant MeSH terms:
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Mesothelioma
Mesothelioma, Malignant
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
 Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Durvalumab
Tremelimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents