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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04300244




Registration number
NCT04300244
Ethics application status
Date submitted
19/02/2020
Date registered
9/03/2020
Date last updated
30/06/2020

Titles & IDs
Public title
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma
Scientific title
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma (the NIPU-study)
Secondary ID [1] 0 0
CA209-7H4 NIPU
Universal Trial Number (UTN)
Trial acronym
NIPU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Cancer, Lung 0 0
Cancer of Lung 0 0
Mesothelioma 0 0
Mesothelioma; Lung 0 0
Mesothelioma; Pleura 0 0
Mesotheliomas Pleural 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - UV1 vaccine + leukine
Other interventions - ipilimumab
Other interventions - nivolumab

Experimental: Arm A - Ipilimumab and nivolumab + UV1

Active Comparator: Arm B - Ipilimumab and nivolumab


Other interventions: 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.

Other interventions: ipilimumab
The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Other interventions: nivolumab
The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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. - 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
Timepoint [1] 0 0
Monitoring for change in imaging evalated tumor lesions indicating progression throughout the trial until 5 years of follow-up has past.
Secondary outcome [1] 0 0
Response evaluation - 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.
Timepoint [1] 0 0
Throughout the trial. Radiological assessments every 6th week during the first year, every 12th week for the next 5 years.
Secondary outcome [2] 0 0
Evaluation of patient reported outcomes (PRO) - 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.
Timepoint [2] 0 0
every other week for the first 12 weeks, every 6th week thereafter
Secondary outcome [3] 0 0
Evaluation of Adverse Events and discontinuation rate of patients - 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.
Timepoint [3] 0 0
Continuously, and until 90 days after discontinuation of study treatment.

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Western Australia - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Aalborg
Country [2] 0 0
Denmark
State/province [2] 0 0
Copenhagen
Country [3] 0 0
Norway
State/province [3] 0 0
Oslo
Country [4] 0 0
Spain
State/province [4] 0 0
Barcelona
Country [5] 0 0
Sweden
State/province [5] 0 0
Lund
Country [6] 0 0
Sweden
State/province [6] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Other
Name
Åslaug Helland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Oslo University Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Ultimovacs ASA
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Bristol-Myers Squibb
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT04300244
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Åslaug Helland, Prof, MD
Address 0 0
Oslo University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Åslaug Helland, Prof, MD
Address 0 0
Country 0 0
Phone 0 0
+47 22934000
Fax 0 0
Email 0 0
ahh@ous-hf.no
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04300244