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

NCT03277209 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 1508016466
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

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.

Conditions

Pancreas Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)

  From baseline through Day 56

Other Outcomes (8)

• Change in T cell distribution within tumour regions within primary or metastatic lesions (e.g. CD3+ T cell accumulation in cancer cell "nests")

  From baseline through Day 56

• Changes in circulating tumour ctDNA levels within plasma, during and after treatment.

  From baseline through Day 56

• Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1), changes in tumour cell populations in samples.

  From baseline through Day 56

Study Arms (1)

All Subjects

EXPERIMENTAL

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

Interventions

Plerixafor DRUG

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

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

Study Sites (2)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Elizabeta Popa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Duncan Jodrell, MD

  Cambridge University Hospitals NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 8, 2017
• Study Start: July 25, 2017
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: March 2, 2020

Record last verified: 2020-02

Locations

US (1); GB (1)