Back to resultsTo Assess the Safety of Continuous IV Administration of Plerixafor and Assess Impact on the Immune Microenvironment in Patients With Pancreatic, Ovarian and Colorectal Adenocarcinomas
Primary Purpose
Pancreas Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Plerixafor
Sponsored by
About this trial
This is an interventional treatment trial for Pancreas Cancer
Eligibility Criteria
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)
Sites / Locations
- Weill Cornell Medical College
- Cambridge University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Subjects
Arm Description
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
Outcomes
Primary Outcome Measures
Causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.
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)
Secondary Outcome Measures
Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)
To explore objective anticancer clinical impact of this strategy.
Full Information
NCT ID
NCT03277209
First Posted
September 6, 2017
Last Updated
February 27, 2020
Sponsor
Weill Medical College of Cornell University
Collaborators
Cambridge University Hospitals NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT03277209
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
terminated due to slow accrual
Study Start Date
July 25, 2017 (Actual)
Primary Completion Date
December 30, 2019 (Actual)
Study Completion Date
December 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Cambridge University Hospitals NHS Foundation Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All Subjects
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Intervention Description
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
Primary Outcome Measure Information:
Title
Causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.
Description
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)
Time Frame
From baseline through Day 56
Secondary Outcome Measure Information:
Title
Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)
Description
To explore objective anticancer clinical impact of this strategy.
Time Frame
From baseline through Day 56
Other Pre-specified Outcome Measures:
Title
Change in T cell distribution within tumour regions within primary or metastatic lesions (e.g. CD3+ T cell accumulation in cancer cell "nests")
Description
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.
Time Frame
From baseline through Day 56
Title
Changes in circulating tumour ctDNA levels within plasma, during and after treatment.
Time Frame
From baseline through Day 56
Title
Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1), changes in tumour cell populations in samples.
Description
To assess modulation of the immune tumour microenvironment following CXCR4 inhibition by plerixafor administration.
Time Frame
From baseline through Day 56
Title
Changes in immune cytokine serum levels.
Time Frame
From baseline through Day 56
Title
T cell receptor (TCR) sequencing in tumour tissue.
Time Frame
From baseline through Day 56
Title
DNA and RNA sequencing in tumour tissue.
Time Frame
From baseline through Day 56
Title
Evidence of systemic pharmacodynamic response to CXCR4i, such as increase in CD34+ cell numbers in blood.
Time Frame
From baseline through Day 56
Title
Correlation between changes in T cell distribution and diurnal cortisol variation.
Time Frame
From baseline through Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeta Popa, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Duncan Jodrell, MD
Organizational Affiliation
Cambridge University Hospitals NHS Foundation Trust
Official's Role
Study Chair
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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