- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT03277209
To Assess the Safety of Continuous IV Administration of Plerixafor and Assess Impact on the Immune Microenvironment in Patients With Pancreatic, Ovarian and Colorectal Adenocarcinomas
27 februari 2020 uppdaterad av: Weill Medical College of Cornell University
To Assess the Safety of Continuous IV Administration of the CXCR4 Antagonist, Plerixafor at Potentially Active Plasma Concentrations and Assess Its Impact on the Immune Microenvironment in Patients With Advanced Pancreatic, High Grade Serous Ovarian and Colorectal Adenocarcinomas
A dose escalation trial to assess the safety of plerixafor in patients with advanced pancreatic, high grade serous ovarian and colorectal cancer.
To identify the proof of mechanism, by demonstrating alterations in T-cell tumour distribution, ideally associated with loss of tumour cells, measured by immunostaining, and changes in FDG uptake.
Studieöversikt
Detaljerad beskrivning
This is a prospective, non-randomised, open label, Phase I, dose escalation trial of plerixafor in patients with histological documentation of advanced pancreatic, high grade serous ovarian or colorectal adenocarcinoma.
We will investigate the feasibility of administering plerixafor in terms of safety, and will try to identify the proof of mechanism in patients.
This trial will follow the standard 3+3, Phase I trial design, leading to a treatment expansion phase to confirm the RP2D.
Studietyp
Interventionell
Inskrivning (Faktisk)
2
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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New York
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New York, New York, Förenta staterna, 10065
- Weill Cornell Medical College
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Cambridge, Storbritannien, CB2 0QQ
- Cambridge University Hospitals NHS Foundation Trust
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Aged 16 years or over (In the US, aged 18 years or over only).
- Dose escalation phase only: Patients with inoperable, histologically proven locally advanced or metastatic pancreatic, high grade serous ovarian or colorectal adenocarcinoma, refractory to conventional chemotherapy or a patient who has declined conventional chemotherapy OR;
- Treatment expansion phase only: Patients with inoperable, histologically proven locally advanced or metastatic pancreatic, refractory to conventional chemotherapy or a patient who has declined conventional chemotherapy.
- Tumour lesions considered to be accessible for core biopsy and immunostaining assessment.
- ECOG performance status 0-1.
- Life expectancy of at least 12 weeks.
- All women of child-bearing potential and all sexually active male patients must agree to use effective contraception methods throughout the trial and for 3 months after the final dose of trial drug.
Exclusion Criteria:
Inadequate haematological function defined by:
- Absolute neutrophil count (ANC) <1.5 x 109/L
- Absolute lymphocyte count <1.0 x 109/L (counts shall be rounded to the nearest tenth. (e.g. 0.96 will be rounded to 1.0 x 109/L))
- Haemoglobin <9.0 g/dL (90 g/L) (may be increased to this level with transfusion as long as there is no evidence of active bleeding)
- Platelets <100 x 109/L
- Clotting; INR >1.3
- Inadequate renal function defined by calculated creatinine clearance by Cockcroft-Gault of <50 ml/min.
Inadequate hepatic function defined by:
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN) or >5 x in the presence of liver metastases
- Total bilirubin >1.5 x ULN
- Current treatment (within 28 days of entry) with chemotherapy, steroids or other immunosuppressive drugs.
- Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the Investigator would place the patient at undue risk or interfere with the trial.
Cardiac co-morbidity:
- Past history of significant rhythm disturbance (e.g. SVT, AF or ventricular irregularities)
- Requirement for pacemaker
- Myocardial infarction in the previous 6 months
- Known medical history of proven postural hypotension.
- Active infection.
- Patients with known allergy to plerixafor or its excipients.
- Patients known to have hepatitis B, hepatitis C or HIV infection.
- Participation in any other interventional clinical trial
- Women, who are pregnant, plan to become pregnant or are lactating (during the trial or for up to 3 months after the last dose)
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: All Subjects
Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr
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Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.
Tidsram: From baseline through Day 56
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Assess safety of continuous IV administration of plerixafor in doses needed to achieve and maintain circulating levels similar to those active in a murine model of PDAC (2 μg/ml)
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From baseline through Day 56
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)
Tidsram: From baseline through Day 56
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To explore objective anticancer clinical impact of this strategy.
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From baseline through Day 56
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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Change in T cell distribution within tumour regions within primary or metastatic lesions (e.g. CD3+ T cell accumulation in cancer cell "nests")
Tidsram: From baseline through Day 56
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To explore relationships between intratumoural T-cell distribution, CXCR4 and CXCL12 immunostaining and other potential biomarkers of immune activation in tissue and blood, such as circulating CD34+ cell counts and diurnal cortisol variation.
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From baseline through Day 56
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Changes in circulating tumour ctDNA levels within plasma, during and after treatment.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1), changes in tumour cell populations in samples.
Tidsram: From baseline through Day 56
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To assess modulation of the immune tumour microenvironment following CXCR4 inhibition by plerixafor administration.
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From baseline through Day 56
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Changes in immune cytokine serum levels.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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T cell receptor (TCR) sequencing in tumour tissue.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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DNA and RNA sequencing in tumour tissue.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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Evidence of systemic pharmacodynamic response to CXCR4i, such as increase in CD34+ cell numbers in blood.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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Correlation between changes in T cell distribution and diurnal cortisol variation.
Tidsram: From baseline through Day 56
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From baseline through Day 56
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Samarbetspartners
Utredare
- Huvudutredare: Elizabeta Popa, MD, Weill Medical College of Cornell University
- Studiestol: Duncan Jodrell, MD, Cambridge University Hospitals NHS Foundation Trust
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
25 juli 2017
Primärt slutförande (Faktisk)
30 december 2019
Avslutad studie (Faktisk)
30 december 2019
Studieregistreringsdatum
Först inskickad
6 september 2017
Först inskickad som uppfyllde QC-kriterierna
6 september 2017
Första postat (Faktisk)
8 september 2017
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
2 mars 2020
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
27 februari 2020
Senast verifierad
1 februari 2020
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Matsmältningssystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Neoplasmer efter plats
- Carcinom
- Neoplasmer, körtel och epitel
- Sjukdomar i det endokrina systemet
- Neoplasmer i matsmältningssystemet
- Neoplasmer i endokrina körtel
- Bukspottkörtelsjukdomar
- Adenocarcinom
- Pankreatiska neoplasmer
- Anti-infektionsmedel
- Antivirala medel
- Anti-HIV-medel
- Antiretrovirala medel
- Plerixafor
Andra studie-ID-nummer
- 1508016466
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Ja
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Ja
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