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

Study Overview

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

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.

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.

Pancreas Cancer

DRUG: Plerixafor

1508016466

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-09-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-02-27
First Submitted that Met QC Criteria 2017-09-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-03-02
First Posted (ACTUAL) 2017-09-08	Results First Posted N/A	Last Verified 2020-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: Plerixafor 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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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

DRUG: Plerixafor

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 Measures	Measure Description	Time Frame
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)	From baseline through Day 56

Secondary Outcome Measures	Measure Description	Time Frame
Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)	To explore objective anticancer clinical impact of this strategy.	From baseline through Day 56

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Cambridge University Hospitals NHS Foundation Trust

Investigators

PRINCIPAL_INVESTIGATOR: Elizabeta Popa, MD, Weill Medical College of Cornell University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record