Combination therapy with Nivolumab and peptide vaccine to patients with metastatic malignant melanoma - an open phase I/II clinical trial to asses safety, immunologic and clinical effect.

Phase 1

• Conditions: Metastatic malignant melanoma; MedDRA version: 21.1Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004527-23-DK
• Lead Sponsor: Center for Cancer Immune Therapy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-11
• Study Completion: 2022-12-31
• Last Update Posted: 30 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1.Age = 16
2.The patient has unrespectable or metastatic melanoma with progressive, persistent or recurrent disease on or following treatment with standard of care agents.
3.The patient is candidate for Nivolumab monotherapy.
4.At least one measurable parameter according to RECIST 1.1.
5.The patient has an ECOG Performance status of 0 or 1.
6.The patient is a female of childbearing potential with negative pregnancy test.
7.Women agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 120 days after the treatment.
8.For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.
9.The patient has met the following hematological and biochemical criteria::
a.AST and ALT =2,5 X ULN or =5 X ULN with liver metastases
b.Serum total bilirubin =1,5 X ULN or direct bilirubin = ULN for patient with total bilirubin level > 1,5 ULN
c.Serum creatinine =1,5 X ULN
d.ANC (Absolute Neutrophil Count) =1,000/mcL
e.Platelets = 75,000 /mcL
f.Hemoglobin = 9 g/dL eller = 5.6 mmol/L

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

1.The patient has previously received monotherapy Nivolumab.
2.The patient has not recovered to grade 0-1 from adverse events due to prior chemotherapy, radioactive or biological cancer therapy.
3.The patient has not recovered from surgery or is less than 4 weeks from major surgery.
4.The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering.
5.The patient is expected to require any other form of systemic antineoplastic therapy while receiving the treatment.
6.The patient has a history of severe clinical autoimmune disease.
7.The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C.
8.The patient requires systemic steroids for management of immune-related adverse events experienced on another immunotherapy.
9.The patient has active CNS metastases and/or carcinomatous meningitis. However patients with subclinical brain metastases < 1 cm can be included (maximum of 4 metastases < 1 cm). (Patients with previously treated brain metastases may participate provided they are clinically stable. Patients with untreated brain metastasis will be excluded).
10.The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders).
11.The patient is pregnant or breastfeeding.
12.The patient is unable to voluntarily agree to participate by signed informed consent or assent.
13.The patient has an active infection requiring systemic therapy.
14.The patient has received a live virus vaccine within 30 days of planned start of therapy.
15.Known side effects to Montanide ISA-51.
16.Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus.
17.Concurrent treatment with other experimental drugs.
18.Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
19.Severe allergy or anaphylactic reactions earlier in life.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To asses safety and tolerability of combination therapy with Nivolumab and the PD-L1/IDO peptide vaccine with the adjuvant Montanide in patients with metastatic malignant melanoma;Secondary Objective: Assess the immunologic response to vaccination with PD-L1/IDO peptide in periferal blood before, during and after treatment. ;Primary end point(s): Safety and tolerability, primary end point will be assessed according to CTCAE version 4.0. ;Timepoint(s) of evaluation of this end point: First evaluation at baseline (prior first vaccination), then before every second subsequent vaccination and finaly during follow up (2 visits)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Development of a measurable vaccine related immune response;Timepoint(s) of evaluation of this end point: Blood samples are drawn at baseline and thereafter every third month.<br>Delayed type hypersensitivity skin test is performed after 6 vaccinations. <br>Tumor biopsies are taken at baseline and after 6 vaccinations.