- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02556463
A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
A Phase I, First-Time-in-Human Study of MEDI9197, a TLR 7/8 Agonist, Administered Intratumorally as a Single Agent in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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Villejuif, Frankrike, 94805
- Research Site
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California
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San Francisco, California, Förenta staterna, 94115
- Research Site
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Colorado
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Aurora, Colorado, Förenta staterna, 80045
- Research Site
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55455
- Research Site
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Missouri
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Saint Louis, Missouri, Förenta staterna, 63110
- Research Site
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New York
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New York, New York, Förenta staterna, 10029
- Research Site
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North Carolina
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Chapel Hill, North Carolina, Förenta staterna, 27599-7305
- Research Site
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19104
- Research Site
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Texas
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Houston, Texas, Förenta staterna, 77030
- Research Site
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Ontario
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Toronto, Ontario, Kanada, M5G 1Z6
- Research Site
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria for All Subjects (Parts 1, 2 and 3)
- Written informed consent and any locally required authorizations.
- Male and female subjects at least 18 years at the time of screening.
- Adequate organ function within 14 days of enrollment confirmed by laboratory results.
- Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
- ECOG 0 or 1.
- Highly effective method of contraception from the date of the screening pregnancy test, and continued precautions for 6 months after the final dose of investigational product.
- Baseline Child-Pugh Score of A1 to B7.
- Life expectancy ≥ 12 weeks, as estimated by Royal Marsden Hospital Score of 0 or 1 at baseline.
Subjects with hepatocellular carcinoma (HCC) are eligible if the tumor is defined as nodular type 1 or 2 only.
Additional Inclusion Criteria for Subjects in Parts 1 and 3
- Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy.
- For subjects with cutaneous/subcutaneous lesions, subjects must have more than one measurable target lesion, at baseline, with a minimum of one lesion that meets protocol specified criteria.
For subjects with deep-seated lesions, subjects must have more than one measurable target lesion at baseline (RECIST v1.1), with a minimum of one deep-seated lesion suitable for image-guided injection and that meets protocol specified criteria.
Additional Inclusion Criteria for Subjects in Part 2 (Closed to Enrollment as of Protocol Amendment 6)
- Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL or unconfirmed diagnosis of CTCL with confirmation biopsy at screening.
- Stage IB, IIA, or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions.
- Previous treatment with at least one standard therapy used to treat the stage of disease at study entry; Stage IB, IIA or IIB CTCL.
- Measurable skin disease with at least 2 lesions amenable to response assessment.
- At least one lesion must be amenable to injection, ie, ≥ 1.5 cm in the longest diameter.
Exclusion Criteria:
Any of the following would exclude the subject from participation in the study:
- Subjects who have received prior immunotherapy [(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL)-1, or programmed cell death 1 antagonists-both require 14 day washout)] are NOT permitted to enroll, with protocol exceptions.
- Pregnant or lactating.
- Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
- Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
- Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
- Requires continuous (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
- History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
- Rapidly progressing disease per protocol.
- Untreated or uncontrolled central nervous system (CNS) involvement.
- Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, with exception of alopecia, vitiligo.
- Uncontrolled concurrent illness.
- Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months, clinical important cardiac arrhythmia, mean QTC interval corrected for heart rate >500ms.
- Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
- Receipt of live, attenuated vaccine within 28 days prior to study entry.
- Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives.
- Cognitive disorder such that informed consent cannot be obtained directly from the subject
- Subjects who have previously participated in this study and received MEDI9197, or concurrent enrollment in another clinical study involving an investigational treatment.
- Subjects who have received prior TLR agonists, both systemic and topical.
- Patients who have received prior therapeutic radiation within 28 days of dosing. All toxicities from prior radiotherapy must have resolved to ≤ Grade 1 or baseline prior to dosing.
- Body weight < 35 kg
- Subjects enrolling in Part 3 (ie, receiving durvalumab) must not have a history of interstitial lung disease or pneumonitis.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Escalation MEDI9197
MEDI9197
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Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)
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Experimentell: Escalation MEDI9197 with durvalumab
MEDI9197 in combination with durvalumab
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Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)
Subjects will receive durvalumab every 4 weeks
Andra namn:
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Experimentell: Escalation MEDI9197 durvalumab radiation
MEDI9197 in combination with durvalumab and palliative radiation
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Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)
Subjects will receive durvalumab every 4 weeks
Andra namn:
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Experimentell: MEDI9197 with palliative radiation
MEDI9197 in combination with palliative radiation
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Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers
Tidsram: From time of informed consent through 4 weeks after last dose of investigational product
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The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
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From time of informed consent through 4 weeks after last dose of investigational product
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Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with CTCL
Tidsram: From time of informed consent through 6 months after last dose of investigational product
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The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
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From time of informed consent through 6 months after last dose of investigational product
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Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.
Tidsram: From time of informed consent through 90 days after last dose of investigational product
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The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
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From time of informed consent through 90 days after last dose of investigational product
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Sekundära resultatmått
Resultatmått |
Tidsram |
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The maximum concentration of MEDI9197 after the first injection
Tidsram: Pre-dose to 24 hours post first dose
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Pre-dose to 24 hours post first dose
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The apparent terminal half-life of MEDI9197
Tidsram: Pre-dose to 24 hours post first dose
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Pre-dose to 24 hours post first dose
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Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue
Tidsram: Baseline to Day 50
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Baseline to Day 50
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Percent change from baseline in serum inflammatory cytokine levels
Tidsram: Pre-dose to end of study, up to 24 months
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Pre-dose to end of study, up to 24 months
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Percent change from baseline in tumor measurements
Tidsram: Pre-dose to disease progression, up to 12 months
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Pre-dose to disease progression, up to 12 months
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Objective response rate
Tidsram: Pre-dose to end of study, up to 24 months
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Pre-dose to end of study, up to 24 months
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Duration of response
Tidsram: Pre-dose to end of study, up to 24 months
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Pre-dose to end of study, up to 24 months
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Percent change from baseline in CAILDS for subjects with CTCL
Tidsram: Pre-dose to disease progression, up to 12 months
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Pre-dose to disease progression, up to 12 months
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Percent change from baseline in mSWAT scored for subjects with CTCL
Tidsram: Pre-dose to disease progression, up to 12 months
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Pre-dose to disease progression, up to 12 months
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Percent change from baseline in Investigator Global Assessment (IGA) for subjects with CTCL
Tidsram: Pre-dose to disease progression, up to 12 months
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Pre-dose to disease progression, up to 12 months
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Percent change from baseline in Subject Global Assessment (SGA) for subjects with CTCL
Tidsram: Pre-dose to disease progression, up to 12 months
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Pre-dose to disease progression, up to 12 months
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Samarbetspartners och utredare
Sponsor
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- D6410C00001
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Kliniska prövningar på MEDI9197
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Valneva Austria GmbHRekryteringZika | ZikavirusinfektionFörenta staterna
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National Institute of Allergy and Infectious Diseases...RekryteringKronisk HIV-infektionFörenta staterna
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International AIDS Vaccine InitiativeNational Institute of Allergy and Infectious Diseases (NIAID); Access to...Har inte rekryterat ännu
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International AIDS Vaccine Initiative3M; Polymun Scientific GmbH; Access to Advanced Health Institute (AAHI)Har inte rekryterat ännu
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National Institute of Allergy and Infectious Diseases...Department of Health and Human Services; HIV Vaccine Trials Network; Inovio... och andra samarbetspartnersAktiv, inte rekryterande
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National Institute of Allergy and Infectious Diseases...Aktiv, inte rekryterandeHIV-1-infektionFörenta staterna
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National Institute of Allergy and Infectious Diseases...Aktiv, inte rekryterande
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National Institute of Allergy and Infectious Diseases...Fred Hutchinson Cancer Center; International AIDS Vaccine Initiative; HIV... och andra samarbetspartnersAktiv, inte rekryterande
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National Institute of Allergy and Infectious Diseases...Duke University; National Institutes of Health (NIH); Department of Health... och andra samarbetspartnersHar inte rekryterat ännu