NCT02588131

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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2015

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2015

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

October 26, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 27, 2015

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

October 27, 2015

Status Verified

October 1, 2015

Enrollment Period

8 months

First QC Date

October 26, 2015

Last Update Submit

October 26, 2015

Conditions

Pleural MesotheliomaPeritoneal Mesothelioma

Keywords

tremelimumabanti-PD-L1 MEDI4736 (Durvalumab)malignant mesothelioma

Outcome Measures

Primary Outcomes (1)

  • immune-related (ir)- objective response rate (ORR)

    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 Outcomes (10)

  • Immune-related-Disease control rate (ir-DCR)

    60 weeks

  • Disease control rate (DCR)

    60 weeks

  • Immune-related-progression-free-survival (PFS)

    60 weeks

  • progression-free-survival (PFS)

    60 weeks

  • Overall survival (OS)

    120 weeks

  • +5 more secondary outcomes

Study Arms (1)

tremelimumab plus MEDI4736

EXPERIMENTAL

Tremelimumab in combination with MEDI4736

Drug: tremelimumab plus MEDI4736

Interventions

tremelimumab plus MEDI4736DRUG

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.

Also known as: MEDI4736 (durvalumab)
tremelimumab plus MEDI4736

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical Oncology and Immunotherapy Division, University Hospital of Siena

Siena, 53100, Italy

RECRUITING

Related Publications (6)

  • Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, Di Giacomo AM, Danielli R, Altomonte M, Mutti L, Maio M. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013 Oct;14(11):1104-1111. doi: 10.1016/S1470-2045(13)70381-4. Epub 2013 Sep 11.

    PMID: 24035405BACKGROUND

  • Calabro L, Ceresoli GL, di Pietro A, Cutaia O, Morra A, Ibrahim R, Maio M. CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy? Cancer Immunol Immunother. 2015 Jan;64(1):105-12. doi: 10.1007/s00262-014-1609-9. Epub 2014 Sep 19.

    PMID: 25233793BACKGROUND

  • Calabro L, Morra A, Fonsatti E, Cutaia O, Fazio C, Annesi D, Lenoci M, Amato G, Danielli R, Altomonte M, Giannarelli D, Di Giacomo AM, Maio M. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med. 2015 Apr;3(4):301-9. doi: 10.1016/S2213-2600(15)00092-2. Epub 2015 Mar 26.

    PMID: 25819643BACKGROUND

  • 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).

    BACKGROUND

  • Calabro L, Rossi G, Morra A, Rosati C, Cutaia O, Daffina MG, Altomonte M, Di Giacomo AM, Casula M, Fazio C, Palmieri G, Giannarelli D, Covre A, Maio M. Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study. Lancet Respir Med. 2021 Sep;9(9):969-976. doi: 10.1016/S2213-2600(21)00043-6. Epub 2021 Apr 9.

    PMID: 33844995DERIVED

  • Calabro L, Morra A, Giannarelli D, Amato G, D'Incecco A, Covre A, Lewis A, Rebelatto MC, Danielli R, Altomonte M, Di Giacomo AM, Maio M. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med. 2018 Jun;6(6):451-460. doi: 10.1016/S2213-2600(18)30151-6. Epub 2018 May 15.

    PMID: 29773326DERIVED

Related Links

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

tremelimumabdurvalumab

Condition Hierarchy (Ancestors)

MesotheliomaAdenomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, MesothelialLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SitePleural NeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Luana Calabro', MD, PhD

    Medical Oncology and Immunotherapy Division, Univeristy Hospital os Siena, Siena, Italy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Luana Calabro', MD, PhD

CONTACT

+39-0577586116l.calabro@ao-siena.toscana.it

Michele Maio, MD, PhD

CONTACT

+39-0577586335mmaiocro@gmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 26, 2015

First Posted

October 27, 2015

Study Start

October 1, 2015

Primary Completion

June 1, 2016

Study Completion

March 1, 2018

Last Updated

October 27, 2015

Record last verified: 2015-10

Locations

IT(1)