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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04300244
Registration number
NCT04300244
Ethics application status
Date submitted
19/02/2020
Date registered
9/03/2020
Date last updated
29/02/2024
Titles & IDs
Public title
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma
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Scientific title
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma (the NIPU-study)
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Secondary ID [1]
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CA209-7H4 NIPU
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Universal Trial Number (UTN)
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Trial acronym
NIPU
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cancer
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Cancer, Lung
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Cancer of Lung
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Mesothelioma
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Mesothelioma; Lung
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Mesothelioma; Pleura
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Mesotheliomas Pleural
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Cancer
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Lung - Non small cell
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Cancer
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Lung - Small cell
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - UV1 vaccine + leukine
Treatment: Other - ipilimumab
Treatment: Other - nivolumab
Experimental: Arm A - Ipilimumab and nivolumab + UV1
Active comparator: Arm B - Ipilimumab and nivolumab
Treatment: Other: UV1 vaccine + leukine
The mode of action of UV1 is to activate the immune system to induce T cells directed against telomerase (hTERT). UV1 vaccination amplifies the pool of hTERT specific tumor-reactive T cells from the naive repertoire and has the potential to increase the breadth and diversity of the tumor-reactive T cell response (epitope spreading). Vaccination with UV1 can thus provide the basis for increased efficacy of checkpoint inhibition therapy, by augmenting the pool of tumor specific T cells in patients with limited or insufficient numbers of T cell clones spontaneously primed by tumor antigens. Reciprocally, the efficacy of UV1 vaccination may be enhanced in combination with checkpoint inhibitors, since the clonal expansion and effector activity of UV1 induced T cells will otherwise be restricted by intrinsic immune regulatory and tumor induced suppressor mechanisms.
Treatment: Other: ipilimumab
The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.
Treatment: Other: nivolumab
The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.
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Intervention code [1]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Evaluation of efficacy of ipilimumab and nivolumab With or without UV1 vaccine in patients With inoperable malignant pleural mesothelioma progressing after first-line platinum-based chemotherapy.
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Assessment method [1]
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Progression-free survival (PFS) per Modified Response Evaluation Criteria in Solid Tumors (RECIST) as determined by blinded independent central review (BICR) assessed by radiologic assessments
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Timepoint [1]
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Monitoring for change in imaging evalated tumor lesions indicating progression throughout the trial until 5 years of follow-up has past.
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Secondary outcome [1]
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Response evaluation
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Assessment method [1]
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Comparison of response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (Modified RECIST), in patients who receive nivolumab and ipilimumab with patients who receive nivolumab and ipilimumab in combination with UV1.
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Timepoint [1]
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Throughout the trial. Radiological assessments every 6th week during the first year, every 12th week for the next 5 years.
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Secondary outcome [2]
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Evaluation of patient reported outcomes (PRO)
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Assessment method [2]
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To evaluate changes from baseline in patient-reported outcomes (PROs) in patients who receive nivolumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1.
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Timepoint [2]
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every other week for the first 12 weeks, every 6th week thereafter
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Secondary outcome [3]
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Evaluation of Adverse Events and discontinuation rate of patients
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Assessment method [3]
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To determine the safety and tolerability of patients receiving ipilimumab and nivolumab With or without UV1 vaccination by monitoring AEs and study drug discontinuation due to AEs.
tolerability in patients who receive nivolumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1, measured by adverse events (AE) and study drug discontinuations due to AEs.
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Timepoint [3]
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Continuously, and until 90 days after discontinuation of study treatment.
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Eligibility
Key inclusion criteria
* Histologically and/or cytologically confirmed malignant pleural mesothelioma.
* Unresectable disease
* Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment (modified RECIST).
* Available unstained archived tumor tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumor block (preferred). NOTE: A fine needle aspiration sample is not sufficient to make the patient eligible for enrollment. Given the complexity of mesothelioma pathological diagnosis , it is expected that they will have a core needle biopsy or surgical tumor biopsy as part of their initial diagnostic work up.
* Age = 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
* Willing to provide archived tumor tissue and blood samples for research.
* Adequate organ function as defined below
1. Haemoglobin = 9.0 g/dL
2. Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
3. Platelet count =100 (or 75) x 109/L (>75,000 per mm3)
4. Serum bilirubin =1.5 x institutional upper limit of normal (ULN).
5. AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN
6. Measured creatinine clearance (CL)
1. >40 mL/min
2. Calculated creatinine CL>40 mL/min (Cockcroft-Gault formula)
3. 24-hour urinecollection for determination of CL
* Males: Creatinine CL (mL/min) =Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
* Females:Creatinine CL (mL/min)=Weight (kg) x (140 - Age)x0.85 72 x serum creatinine (mg/dL)
* Previously treated with at least one line of platinum -pemetrexed
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Disease suitable for curative surgery
* Previous treatment with a PD-1 or PD-L1 inhibitor, including nivolumab or any other agent targeting immune checkpoints.
* Non-pleural mesothelioma e.g. mesothelioma arising in peritoneum, tunica vaginalis or any serosal surface other than the pleura.
* Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.
* Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone >10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose >10 mg prednisone equivalent) must have been completed = 2 weeks prior to registration.
* Uncontrolled seizures.
* Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, 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. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded.
* History of primary immunodeficiency.
* History of allogeneic organ transplant.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
* Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion.
* Known history of leptomeningeal carcinomatosis.
* Pregnant or lactating women
* Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving nivolumab.
* Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results.
* History of allergy or hypersensitivity to any of the active substances or excipients in the study drug.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/05/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
15/03/2027
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Actual
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Sample size
Target
118
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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University of Western Australia - Perth
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Recruitment postcode(s) [1]
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- Perth
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Recruitment outside Australia
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Denmark
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State/province [1]
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Aalborg
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Denmark
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Copenhagen
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Norway
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State/province [3]
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Oslo
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Spain
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State/province [4]
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Barcelona
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Sweden
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State/province [5]
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Lund
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Country [6]
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Sweden
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State/province [6]
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Stockholm
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Funding & Sponsors
Primary sponsor type
Other
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Name
Åslaug Helland
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Oslo University Hospital
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Address [1]
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Other collaborator category [2]
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Commercial sector/industry
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Name [2]
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Ultimovacs ASA
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Address [2]
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Other collaborator category [3]
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Commercial sector/industry
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Name [3]
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Bristol-Myers Squibb
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Address [3]
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Ethics approval
Ethics application status
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Summary
Brief summary
The objective of the study is to induce a meaningful progression-free survival benefit in patients with Malign Pleural Mesothelioma (MPM) after progression on first line standard platinum doublet chemotherapy, by treating with nivolumab and ipilimumab with or without UV1 vaccine.
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Trial website
https://clinicaltrials.gov/study/NCT04300244
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Trial related presentations / publications
Haakensen VD, Nowak AK, Ellingsen EB, Farooqi SJ, Bjaanaes MM, Horndalsveen H, Mcculloch T, Grundberg O, Cedres SM, Helland A. NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma. J Transl Med. 2021 May 31;19(1):232. doi: 10.1186/s12967-021-02905-3.
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Public notes
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Contacts
Principal investigator
Name
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Åslaug Helland, Prof, MD
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Address
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Oslo University Hospital
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Phone
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Fax
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Email
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04300244
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