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NCT03665545 | SNCTP000003000

Pour les patients souffrant de tumeur au cerveau récidivant : traitement avec deux immunothérapies pour stimuler le système immunitaire

Data source: BASEC (Imported from 16.08.2019), WHO (Imported from 04.08.2019)
Changed: 14.08.2019
Disease category: Anderer Krebs

Brief description of trial (Source of data: BASEC)

Le médicament IMA950 est un vaccin qui vise à stimuler votre système immunitaire pour combattre votre tumeur. Le Poly-ICLC est une substance dite adjuvante permettant de renforcer l’effet du médicament. Le pembrolizumab est un anticorps qui potentialise les réponses des cellules immunitaires dénommés lymphocytes T, y compris les réponses anti-tumorales. Dans cette étude, vous serez assigné(e) au hasard à l'un des deux groupes (bras) de traitement : vous pouvez recevoir soit l’IMA950 et le Poly-ICLC (bras 1) soit l’IMA950 et le Poly-ICLC en combinaison avec le pembrolizumab (bras 2). IMA950 et Poly-ICLC seront administrés par injection sous la peau (en sous-cutané), le pembrolizumab par voie intraveineuse. Environ 24 patients participeront à cette étude qui durera approximativement 3 ans. L’étude est menée par les Hôpitaux Universitaires de Genève (HUG).

Health conditions investigated (Source of data: BASEC)

Tumeur cérébrale appelée glioblastome, un cancer hautement agressif pour lequel il n'existe à ce jour pas de traitement standard curatif.

Health conditions (Source of data: WHO)

Glioblastoma Multiforme;Glioblastoma, Adult;Glioma of Brain

Rare disease (Source of data: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Nous procéderons à des examens préliminaires d’inclusion avant le début du traitement. Le protocole de traitement avec IMA950 et Poly-ICLC s’étale à partir de 6 semaines (un mois et demi) avant l’intervention chirurgicale – le cas échéant - (phase d’induction) jusqu’à la 18ème semaine après l’intervention chirurgicale (quatre mois et demi). Vous allez recevoir 4 vaccinations IMA950 (avec Poly-ICLC) pendant la phase d’induction (jour 1, jour 8, jour 15 et jour 22) et 5 vaccinations pendant la phase de maintenance. Si vous êtes assigné(e) au bras 2 (traitement avec Pembrolizumab), vous allez également recevoir du pembrolizumab pendant la phase d’induction (2 et 5 semaines avant l’intervention chirurgicale) ainsi que pendant la phase de maintenance (une injection à la 3ème semaine après l’intervention et après toutes les trois semaines, jusqu’à une possible progression tumorale et en absence d’effets secondaires graves). On effectuera des IRM cérébrales : pendant la période d’évaluation (avant le début du traitement), 24-48 heures après l’intervention chirurgicale et tous les deux mois après l’intervention. Les examens suivants seront effectués: prise de sang standard à chaque vaccination IMA950 et/ou injection de Pembrolizumab (au total 40 ml correspondants à 8 cuillères à soupe pour chaque prélèvement sanguin), examen clinique le jour du traitement et évaluation de votre capacité à effectuer des activités quotidiennes. Afin d’analyser la réaction immunitaire au traitement, en total 7 prises de sang d’environ 120ml (l’équivalent de 24 cuillères à soupe) seront effectuées (deux avant le début du traitement, une pendant la phase d’induction et quatre pendant la phase de maintenance). Trois prélèvements supplémentaires seront aussi faits en fin de traitement et dans le suivi post-traitement.

Interventions (Source of data: WHO)

Drug: IMA950/Poly-ICLC

Criteria for participation in trial (Source of data: BASEC)

1) Vous êtes atteint(e) d’une tumeur cérébrale appelée glioblastome (le diagnostic a été confirmé par des tests pathologiques).

2) Glioblastome en rechute (première rechute ou suivante).

3)Test sanguin appelé phénotypage HLA (typage human leukocyte
antigen) positif (test à partir d’un échantillon de sang). Ce test permet de déterminer les molécules protéiques qui sont utilisées pour la reconnaissance immunitaire. Chaque individu présente des molécules HLA différentes, mais seules les molécules de type HLA-A*0201 peuvent porter les peptides du vaccin IMA950 et donc stimuler votre système immunitaire. Dès lors, le traitement par le vaccin IMA950 peut être bénéfique pour vous uniquement dans le cas où vous présentez l’allèle HLA-A2 (HLA-A*0201).

Exclusion criteria (Source of data: BASEC)

1) Toute autre vaccination administrée dans les 2 semaines précédants la première vaccination d'étude IMA950.

2) Diagnostic d'immunodéficience ou de maladie auto-immune active nécessitant d’un traitement systémique au cours des 3 derniers mois ou un antécédent documenté de maladie auto-immune cliniquement sévère.

3) Une autre tumeur maligne connue qui progresse ou nécessite un traitement actif.

Inclusion/Exclusion Criteria (Source of data: WHO)


1. Histological documentation of glioblastoma (de novo or secondary GBM). Patients will
an initial diagnosis of a grade 3 glioma that have unequivocal radiologic evidence of
high-grade disease progression (i.e. indication of secondary GBM transformation) will
be eligible for inclusion.

2. Patient must be at first or subsequent relapse.

3. HLA-A*0201 positive patients (after pre-screening).

4. ECOG performance status of 0 or 1.

5. Age > 18 years, life expectancy of least 4 months.

6. Patient must be on stable or decreasing dose of steroids, with a maximal dose of
Dexamethasone of 4mg/day or equivalent.

7. Adequate bone marrow, liver and kidney function (see Table 2 for definition).

8. Negative Hepatitis B serology (HBcAg-seronegative).

9. Capable of co-operating with the protocol schedule of Pembrolizumab combined with
IMA950 and Poly-ICLC and follow-up.

10. Have measurable disease according to the iRANO criteria. Tumor lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions.

11. Be willing and able to provide written informed consent for the trial.

12. Be willing to provide tissue from a study-specific biopsy of a tumor lesion.

13. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. A
urine test can be considered if the serum test is not available.

14. Female subjects of childbearing potential (Section 5.6.2) must be willing to use 2
methods of contraception or be surgically sterile, or abstain from heterosexual
activity as outlined in Section 5.6.2 - Contraception, for the course of the study
through 120 days after the last dose of study medication. Subjects of childbearing
potential are those who have not been surgically sterilized or have not been in
menopause for more than one year.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.

15. Male subjects of childbearing potential must agree to use an adequate method of
contraception as outlined in Section 5.6.2- Contraception, starting with the first
dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.

5.1.4. Main Study Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

1. Any other vaccination given within 2 weeks before first IMA950 vaccination.

2. Diagnosis of immunodeficiency or active autoimmune disease requiring systemic
treatment within the past 3 months or a documented history of clinically severe
autoimmune disease, or a condition that requires systemic steroids (> 10mg/day
prednisone or equivalent) or immunosuppressive agents. Replacement therapy (eg.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of systemic treatment.

3. Patients with evidence of history bleeding diathesis.

4. Pregnant or breastfeeding patients, or expecting to conceive or father children within
the projected duration of the trial, starting with the pre-screening or screening
visit through 120 days after the last dose of trial treatment.

5. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

6. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.

7. Has a known history of active TB (Bacillus Tuberculosis)

8. Hypersensitivity to pembrolizumab or any of its excipients.

9. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or
who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to
agents administered more than 4 weeks earlier.

10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent.

Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may
qualify for the study.

Note: If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.

11. Has known history of, or any evidence of active (non-infectious) pneumonitis that
required(s) steroids.

12. Has an active infection requiring systemic therapy.

13. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.

14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

17. Has known past or active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
RNA [qualitative] is detected). Only patients with negative serology for past or
current exposure to HBV and HCV will be eligible.

18. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03665545

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03665545

Further information on trial

Date trial registered

01.09.2018

Incorporation of the first participant

25.10.2018

Recruitment status

Recruiting

Academic title (Source of data: WHO)

Pembrolizumab in Association With the Multipeptide Vaccine IMA950 Adjuvanted With Poly-ICLC for Relapsing Glioblastoma: a Randomized Phase I/ II Trial

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Source of data: WHO)

Phase 1/Phase 2

Primary end point (Source of data: WHO)

Incidence of Treatment-Emergent Adverse Events

Secundary end point (Source of data: WHO)

Patient-reported Quality of life;Overall Survival

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Genf

Countries (Source of data: WHO)

Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Prof Pierre-Yves Dietrich
+41223729861
Pierre-Yves.Dietrich@hcuge.ch

Contact for general information (Source of data: WHO)

Pierre-Yves Dietrich, Prof.;Aurélie VUILLEUMIER, Dr
University Hospital, Geneva
+41795535100
Aurelie.Vuilleumier@hcuge.ch

Contact for scientific information (Source of data: WHO)

Pierre-Yves Dietrich, Prof.;Aurélie VUILLEUMIER, Dr
University Hospital, Geneva
+41795535100
Aurelie.Vuilleumier@hcuge.ch

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

University Hospital, Geneva

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2018-00718

Secondary ID (Source of data: WHO)

MK3475-480