Clinical Trials Register

Summary
EudraCT Number:	2014-000117-31
Sponsor's Protocol Code Number:	CAM-PLEX
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-07-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2014-000117-31

A.3

Full title of the trial

To assess the safety of continuous IV administration of the CXCR4 antagonist, plerixafor (Mozobil), 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.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study in patients with unresectable or metastatic pancreatic, high grade serous ovarian or colorectal cancer using the drug plerixafor, with the goal of finding out the correct dose of the study drug to give, and, to find out if the study drug causes the same changes in participants that has been seen in laboratory experiments.

A.3.2

Name or abbreviated title of the trial where available

CAM-PLEX

A.4.1

Sponsor's protocol code number

CAM-PLEX

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02179970

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-aventis Groupe
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Stand Up To Cancer and the Lustgarten Foundation
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Cancer Research UK
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	NIHR Biomedical Research Centre
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Experimental Cancer Medicine Centre
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
B.5.2	Functional name of contact point	Mrs Carrie Bayliss
B.5.3	Address:
B.5.3.1	Street Address	Cambridge Clinical Trials Unit, Addenbrookes Hospital, Level 6, Coton House, Box 401
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB2 0QQ
B.5.3.4	Country	United Kingdom
B.5.5	Fax number	01223256763
B.5.6	E-mail	cctu@addenbrookes.nhs.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Plerixafor
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	plerixafor
D.3.9.1	CAS number	110078-46-1
D.3.9.3	Other descriptive name	Plerixafor Free Base
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pancreatic adenocarcinoma
High grade serous ovarian adenocarcinoma
Colorectal adenocarcinoma

E.1.1.1

Medical condition in easily understood language

Pancreatic cancer
Ovarian cancer
Colorectal cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10061451
E.1.2	Term	Colorectal cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10033604
E.1.2	Term	Pancreatic cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To 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)

E.2.2

Secondary objectives of the trial

Secondary objectives
• To explore objective anticancer clinical impact of this strategy.

Exploratory objectives
• To assess modulation of the immune tumour micro¬environment following CXCR4 inhibition by plerixafor administration.
• 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 markers of immune activation.
• Changes in circulating tumour (ct) DNA levels within plasma, during and after treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients are eligible for inclusion in the study if they meet all of the following criteria:

• Aged 16 years or over.
• 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;
• 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 study and for 3 months after the final dose of study drug.

E.4

Principal exclusion criteria

Patients are to be excluded from the study if they meet any of the following criteria:

• Inadequate haematological function defined by:
o Absolute neutrophil count (ANC) <1.5 x 109/L
o Absolute lymphocyte count < normal level for institution
o 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)
o Platelets <100 x 109/L
o Clotting; INR >1.3
• Inadequate renal function defined by calculated creatinine clearance by Cockcroft-Gault of <50 ml/min.
• Inadequate hepatic function defined by:
o 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
o 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 judgement of the Investigator would place the patient at undue risk or interfere with the study.
• Cardiac co-morbidity:
o Past history of significant rhythm disturbance (e.g. SVT, AF or ventricular irregularities)
o Requirement for pacemaker
o Myocardial infarction in the previous 6 months
o 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 study or for up to 3 months after the last dose)
• Men who plan to father a child within 3 months after the last dose

E.5 End points

E.5.1

Primary end point(s)

• Safety and tolerability: Determining the causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.

• The plasma pharmacokinetics of plerixafor in patients with cancer. Css ≥2 µg/ml should be achieved in ≥80% of patients treated at the RP2D.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will undergo daily Adverse Event assessments whilst they are receiving study drug treatment. All AEs and SAEs will be graded according to NCI CTCAE v.4.03.

Patients will have research blood samples taken for PK at screening and on Days 2, 4 and 8.

E.5.2

Secondary end point(s)

Secondary endpoints:
• Objective data on disease status to assess response at day 28.
• Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)

Exploratory endpoints:
• Change in T cell distribution within tumour regions within primary or metastatic lesions (CD3+ T cell accumulation in cancer cell “nests”)
• Changes in circulating tumour ctDNA levels within plasma, during and after treatment.
• Evaluation of CXCR4 receptor occupancy on circulating T cells.
• Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1 and Annex in V), changes in tumour cell populations in samples.
• Evidence of systemic pharmacodynamic response to CXCR4i, such as increase in CD34+ cell numbers in blood.

E.5.2.1

Timepoint(s) of evaluation of this end point

Disease status will be evaluated from the Day 28 CT scan and RECIST report.

All other endpoints will be investigated after the end of the trial.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose escalation

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1