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

October 26, 2015 updated by: Italian Network for Tumor Biotherapy Foundation

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Siena, Italy, 53100
        • Recruiting
        • Medical Oncology and Immunotherapy Division, University Hospital of Siena
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • MEDI4736 (durvalumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
60 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
60 weeks
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
60 weeks
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
60 weeks
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
60 weeks
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.
120 weeks
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
120 weeks
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.
60 weeks
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
60 weeks
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
60 weeks
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.
120 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italian Network for Tumor Biotherapy Foundation

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Luana Calabro', MD, PhD, Medical Oncology and Immunotherapy Division, Univeristy Hospital os Siena, Siena, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Anticipated)

June 1, 2016

Study Completion (Anticipated)

March 1, 2018

Study Registration Dates

First Submitted

October 26, 2015

First Submitted That Met QC Criteria

October 26, 2015

First Posted (Estimate)

October 27, 2015

Study Record Updates

Last Update Posted (Estimate)

October 27, 2015

Last Update Submitted That Met QC Criteria

October 26, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIBIT-MESO-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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