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Malignant Pleural MesotheliomaPhase 2INITIATENCT03048474

Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma

A Phase 2 study testing nivolumab and ipilimumab in people with Malignant Pleural Mesothelioma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, monocenter, single arm, phase II trial in 33 patients with unresectable MPM, who experience disease progression or recurrence after at least one previous line of platinum-based systemic treatment. Nivolumab will be administered at a fixed dose of 240 mg every 2 week. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Pleural Mesothelioma
What is being tested?
nivolumab and ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteNetherlands
Study dates
Sep 2016to Dec 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent form
  • Age ≥ 18 years
  • WHO-ECOG performance status 0 or 1
  • Able to comply with the study protocol, in the investigator's judgment
  • Patients with histologically confirmed diagnosis of the recurrence of MPM. Any pleural MPM subtype is permitted for inclusion in the study
  • Progressive disease after at least one prior systemic treatment with a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM. All prior cytotoxic toxicities must have resolved to grade ≤ 1 prior to registration
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  • Measurable disease on CT scan, according to modified RECIST Criteria for Mesothelioma (Byrne MJ, 2004)
  • Life expectancy ≥ 12 weeks
  • Adequate hematologic and organ function, defined by the following laboratory results, obtained within 14 days prior to the first study treatment:
  • Absolute neutrophil count (ANC) ≥ 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
  • WBC count ≥ 3000 cells/µL
  • Lymphocyte count ≥ 250 cells/µL
  • Platelet count ≥ 100.000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
  • Hemoglobin ≥ 5.6 mmol/L
  • Serum albumin ≥ 25 gr/L
  • AST, ALT and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions: patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled
  • INR and aPTT ≤ 1.5 x ULN Patients receiving therapeutic anticoagulation should be on a stable dose Creatinine clearance ≥ 45 mL/min Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration or Modification of Diet in Renal Disease formulae may be used; 24-hour urine collection is not required
  • Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) and men with partners of childbearing potential, must agree to use adequate contraception (double barrier birth control) for the whole duration of study treatment and for 3 months after the last dose of therapy
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 48 hours prior the first dose of treatment

Who cannot join

  • Medical or psychological impediment to comply with the protocol
  • Patients with only peritoneal MPM
  • Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for at least five years
  • Concomitant participation in another clinical trial (by the investigator's judgment)
  • Uncontrolled pleural/peritoneal effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrolment.
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  • Previous treatment with any checkpoint inhibitor
  • Pregnant or lactating women
  • Patients with brain metastases
  • History of or active autoimmune disease (e.g. pneumonitis; rheumatoid arthritis; severe form of psoriasis; uncontrolled type I diabetes or hypothyroidism)
  • History of idiopathic pulmonary fibrosis (including pneumonitis) or unresolved drug-induced pneumonitis, organizing pneumonia, or active pneumonitis on screening chest CT scan
  • History of relevant gastrointestinal disease, including, but not limited to, Crohn's disease, ulcerative colitis, recurrent diverticulitis
  • Prior allogenic bone marrow transplantation or prior solid organ transplantation
  • History of HIV
  • Patients with history of HBV infection are eligible if serological profile is compatible with past/resolved infection (defined as negative HBsAg test and positive antibody to HBV core antigen [anti-HBc] antibody test) and HBsAg test and HBV-DNA are both negative prior to Cycle 1, Day 1
  • Patients with history of HCV infection must be screened for HCV-RNA PCR test prior to Cycle 1, Day 1, and are eligible if the test turns negative
  • Other serious concomitant disease, including:
  • Active tuberculosis Severe infections within 4 weeks prior to Cycle 1, Day 1 Significant cardiovascular disease (NYHA class III or IV), myocardial infarction within the previous 6 months, unstable angina, or unstable arrhythmias Significant pulmonary (asthma or COPD) or hepatic disease or other illness considered by the investigator to constitute an unwarranted high risk for investigational treatment
  • Major surgical procedures within 28 days prior to Cycle 1, Day 1
  • Concurrent medications Treatment with systemic immunosuppressive medications, including but not limited to prednisone (with specific exceptions; see below), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
  • The use of systemic prednisone at the dosage of 10 mg/day or lower (or equivalent) is allowed.
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Netherlands Cancer Institute-Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam, North Holland, 1066CX

Other trials in Netherlands

About this study

Official title: Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma: a Phase II Study. Acronym: INITIATE

This is a prospective, monocenter, single arm, phase II trial in 33 patients with unresectable MPM, who experience disease progression or recurrence after at least one previous line of platinum-based systemic treatment.

Nivolumab will be administered at a fixed dose of 240 mg every 2 week. Nivolumab will be given in combination with ipilimumab on week 1, 7, 13 and 19 and will be administered prior to the infusion of ipilimumab. Ipilimumab will be administered at the dose of 1 mg/Kg.The patients will receive nivolumab monotherapy on week 3, 5, 9, 11, 15 and 17. From week 21 thereafter, Nivolumab will be then administered every 2 weeks for a maximum period of 2 years or until disease progression or unacceptable toxicity occurs.

Read the detailed description

Patients will undergo pre- and post-treatment thoracoscopies/biopsies.

Being tested
nivolumab and ipilimumab
Keywords
progressive disease after at least 1 course of chemotherapy
Medical subject headings
Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nivolumab and ipilimumabDrug

    Also called BMS-936558 and L01XC11

Study groups in NCT03048474
Study groupRoleWhat they receive
Nivolumab and IpilimumabExperimentalNivolumab will be administered at a fixed dose of 240 mg every 2 weeks for a maximum period of 2 years. Nivolumab will be given in combination with ipilimumab on week 1, 7, 13 and 19. Ipilimumab will be administered at the dose of 1 mg/Kg.
Receives: Drug: nivolumab and ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Controle Rate (DCR) at 12 weeks

    The number of patients that have CR or PR plus the number of patients with stable disease as a percentage of the total number of patients in the study.

    Measured: at 12 weeks

Secondary outcomes (5)

  1. Safety: the incidence of adverse events, serious adverse events, deaths and laboratory abnormalities.

    Incidence of (serious) adverse events, serious adverse events, deaths and laboratory abnormalities.

    Measured: Participants will be followed for the duration of the trial, an expected average of 6 weeks

  2. Disease Controle Rate (DCR) at 6 months

    The number of patients that have CR or PR plus the number of patients with stable disease as a percentage of the total number of patients in the study.

    Measured: at 6 months

  3. Progression Free Survival (PFS)

    The time from the date of start treatment to the date of the first documented tumor progression as determined by modified RECIST, or death due to any cause

    Measured: Until progression, every 6 weeks up to 48 weeks

  4. Overall Survival (OS)

    The time from date of start of treatment to the date of death from any cause, every 6 weeks up to 48 weeks, thereafter every 12 weeks up to 36 months

    Measured: every 6 weeks up to 48 weeks, thereafter every 12 weeks up to 36 months.

  5. Overall Response Rate (ORR)

    The number of subjects whose best confirmed objective response is a CR or PR, divided by the number of treated subjects

    Measured: Every 6 weeks up to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2017 (estimated)
  2. Study startSep 2016
  3. Primary completionDec 2017
  4. Study completionDec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03048474
Sponsor's protocol ID
N16INM
Acronym
INITIATE
Status last verified
Jan 2021
First submitted
24 Oct 2016
Last updated
20 Jan 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Desai AP, Kosari F, Disselhorst M, Yin J, Agahi A, Peikert T, Udell J, Johnson SH, Smadbeck J, Murphy S, Karagouga G, McCune A, Schaefer-Klein J, Borad MJ, Cheville J, Vasmatzis G, Baas P, Mansfield A. Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy. J Immunother Cancer. 2023 Jun;11(6):e006035. doi: 10.1136/jitc-2022-006035.

    PubMed 37279993

  • Mankor JM, Disselhorst MJ, Poncin M, Baas P, Aerts JGJV, Vroman H. Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials. EBioMedicine. 2020 Dec;62:103040. doi: 10.1016/j.ebiom.2020.103040. Epub 2020 Nov 7.

    PubMed 33166791

  • Disselhorst MJ, Quispel-Janssen J, Lalezari F, Monkhorst K, de Vries JF, van der Noort V, Harms E, Burgers S, Baas P. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019 Mar;7(3):260-270. doi: 10.1016/S2213-2600(18)30420-X. Epub 2019 Jan 16.

    PubMed 30660511

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nivolumab and ipilimumab in people with Malignant Pleural Mesothelioma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Controle Rate (DCR) at 12 weeks (time frame: at 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03048474, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.

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