| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic malignant melanoma |
| Metastatisk malignt melanom |
|
| E.1.1.1 | Medical condition in easily understood language |
| Malignant melanoma with metastatic disease |
| Modermærkekræft med spredning |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10027480 |
| E.1.2 | Term | Metastatic malignant melanoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 |
| Vurdere sikkerhed og tolerabilitet ved kombinationsbehandling med Nivolumab og PD-L1/IDO peptid vaccine med adjuvanten Montanid til patienter med metastatisk malignt melanom |
|
| E.2.2 | Secondary objectives of the trial |
| Assess the immunologic response to vaccination with PD-L1/IDO peptide in periferal blood before, during and after treatment. |
| Karakterisere immunresponser til vaccination med PD-L1 peptid i perifert blod før, under og efter behandlingen. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
|
1. Alder ≥ 16
2. Patienten har metastatisk melanom med progressiv eller tilbagevendende sygdom efter behandling med standard terapi.
3. Patienten er kandidat til Nivolumab monoterapi.
4. Mindst én målbar parameter ifølge RECIST 1.1.
5. Patienten har ECOG performance status på 0 eller 1.
6. Patienten er en kvinde i den fertile alder med negativ graviditetstest.
7. Kvinder skal bruge prævention med en fejlprocent på <1% om året i behandlingsperioden og i mindst 120 dage efter behandlingen.
8. For mænd: aftale om at bruge prævention og aftale om at afstå fra at donere sæd.
9. Patienten har opfyldt følgende hæmatologiske og biokemiske kriterier:
a. AST og ALT ≤2,5 X ULN eller ≤5 x ULN med levermetastaser
b. Serum total bilirubin ≤1,5 X ULN eller direkte bilirubin ≤ ULN for patient med total bilirubin niveau> 1,5 ULN
c. Serum kreatinin ≤1,5 X ULN
d. ANC (absolut neutrofile tal) ≥1,000 / mcL
e. Trombocytter ≥ 75.000 / mcL
f. Hæmoglobin ≥ 9 g / dl or ≥ 5,6 mmol |
|
| E.4 | Principal 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.
|
1. Patienten har tidligere modtaget monoterapi Nivolumab.
2. Patienten er ikke genvundet til grad 0-1 bivirkninger på grund af tidligere kemoterapi, radioaktivt eller biologisk kræftbehandling.
3. Patienten er ikke kommet sig fra kirurgi eller er mindre end 4 uger fra større kirurgi.
4. Patienten har en historie med livstruende eller alvorlige immun bivirkninger i behandling med anden immunterapi og anses for at være i risiko for ikke at komme sig over behandlingen.
5. Forventer at patienten får behov for andre former for systemisk antineoplastisk terapi, mens de får behandlingen.
6. Patienten har en historie med alvorlig klinisk autoimmun sygdom.
7. Patienten har en historie med pneumonitis, organtransplantation, human immundefekt virus positiv, aktiv hepatitis B eller hepatitis C.
8. Patienten kræver systemiske steroider til styring af immun-relaterede bivirkninger oplevet på en anden immunterapi.
9. Patienten har aktive CNS-metastaser og / eller carcinomatøs meningitis. Men patienter med subklinisk hjernemetastaser <1 cm kan medtages (maksimalt 4 metastaser <1 cm). (Patienter med tidligere behandlede hjernemetastaser kan deltage forudsat at de er klinisk stabile. Patienter med ubehandlede hjernemetastaser vil blive udelukket).
10. Patienten har enhver tilstand, der vil forstyrre patientefterlevelse eller sikkerhed (men ikke begrænset til psykiatriske eller stofmisbrug lidelser).
11. Patienten er gravid eller ammer.
12. Patienten er ude af stand til frivilligt at acceptere at deltage ved underskrevet informeret samtykke eller samtykke.
13. Patienten har en aktiv infektion, der kræver systemisk behandling.
14. Patienten har fået en levende virus vaccine indenfor 30 dage inden planlagt behandlingsstart.
15. Kendte bivirkninger til Montanid ISA-51.
16. Væsentlig medicinsk lidelse ifølge investigator; f.eks. svær astma eller kronisk obstruktiv lungesygdom, dysreguleret hjertesygdom eller dysreguleret diabetes mellitus.
17. Samtidig behandling med andre eksperimentelle lægemidler.
18. Eventuelle aktive autoimmune sygdomme, f.eks autoimmun neutropeni, thrombocytopeni eller hæmolytisk anæmi, systemisk lupus erythematosus, sklerodermi, myasthenia gravis, autoimmun glomerulonephritis, autoimmun adrenal mangel, autoimmun thyroiditis etc.
19. Alvorlige allergi eller anafylaktiske reaktioner tidligere i livet. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Safety and tolerability, primary end point will be assessed according to CTCAE version 4.0. |
| Sikekrhed og tolerabilitet. Primære endepunkter vil blive klassificeret i henhold til CTCAE version 4.0. |
|
| E.5.1.1 | 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) |
| Første evaluering ved opstart (før første vaccination), derefter før hveranden følgende vaccinationer og slutteligt ved de 2 opfølgende besøg. |
|
| E.5.2 | Secondary end point(s) |
| Development of a measurable vaccine related immune response |
| Udvikling af et målbart vaccineinduceret immunrespons |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples are drawn at baseline and thereafter every third month.
Delayed type hypersensitivity skin test is performed after 6 vaccinations.
Tumor biopsies are taken at baseline and after 6 vaccinations. |
Blodprøver til immunmonitorering udtages før behandlingsstart og efterfølgende hver 3 måned.
Delayed type hypersensitivity hudtest foretages efter 6 vaccinationer.
Tumor biopsier tages før behandlingsstart og efter 6 vaccinationer. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| First time combining Nivolumab with the PD-L1/IDO peptide vaccine |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
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