The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613001061729
Ethics application status
Approved
Date submitted
23/08/2013
Date registered
23/09/2013
Date last updated
23/09/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Open-Label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CX-5461 in Patients with Advanced Haematologic Malignancies
Scientific title
A Phase 1, Open-Label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CX-5461 in Patients with Advanced Haematologic Malignancies
Secondary ID [1] 282946 0
Peter MacCallum Cancer Centre Protocol No. PMCC 12/79
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Any advanced Haematologic Malignancy 289770 0
Condition category
Condition code
Cancer 290113 290113 0 0
Myeloma
Cancer 290116 290116 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 290117 290117 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I study of CX-5461, an RNA polymerase I inhibitor. 40 patients with histologically confirmed relapsed or refractory advanced haematologic malignancies, who have progressed following at least one prior treatment regimen, will be enrolled in the study. CX-5461 will be administered by intravenous infusion over 1 hour every 21 days. Seven dose levels are planned: 25 mg/m2, 50 mg/m2, 100 mg/m2, 170 mg/m2, 250 mg/m2, 330 mg/m2and 450 mg/m2 per dose. Patients will be assigned to a dose level in the order of study entry. Patients may continue to receive an infusion of CX-5461 every 3 weeks until disease progression, occurance of unacceptable toxicities, or the decision of the patient and/or Investigator.
Intervention code [1] 287653 0
Treatment: Drugs
Comparator / control treatment
No Comparator
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290147 0
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenously administered CX-5461 when used intravenously in haematologic cancers. DLTs will be assessed by physical exam and clinical laboratory blood tests.
Timepoint [1] 290147 0
Dose limiting toxicities will be assessed during the first cycle only, on Days 1, 2, 3, 4, 8, 15 and at the end of the 3 week cycle.
Secondary outcome [1] 304017 0
To establish the safety profile of CX-5461 at the MTD. Adverse events (e.g. fatigue, infections and bleeding) are graded using the Common Terminology Criteria for Adverse Events (CTCAE), Version 4. Comparison of vital sign measurements, physical examination assessments, Eastern Cooperative Oncology Group (ECOG) performance assessments, electrocardiogram (ECG), clinical laboratory tests for haematology, coagulation and biochemistry from baseline to study completion. Possible side effects may vary depending on the dose received but are expected to be reversible.
Timepoint [1] 304017 0
Adverse events will be monitored for the duration of study (Cycle 1 will be assessed at days 1, 2, 3, 4, 8, 15 and end of cycle; subsequent cycles will be assessed at day 1 of each cycle and at the end of study treatment)
Secondary outcome [2] 304018 0
To establish the pharmacokinetic (PK) profile of CX-5461.
Timepoint [2] 304018 0
Blood samples will be collected for PK analysis on Days 1, 2, 3 and 4 of the 1st treatment cycle.
Secondary outcome [3] 304020 0
To observe patients for preliminary antitumor activity of CX-5461.
Timepoint [3] 304020 0
Response will be measured on D14 to D18 of Cycle 2, and alternate cycles therafter, using clinical assessments, imaging and laboratory tests for the duration of the study.
Secondary outcome [4] 304021 0
To evaluate the mechanism of action of CX-5461 in haematologic cancers and to identify predictive biomarkers of efficacy in human haematologic cancers.
Timepoint [4] 304021 0
Blood and tissue samples will be collected at scheduled timepoints for the duration of the study. The scheduled timepoints are D1 and D2 of Cycle 1, D1 of Cycle 2 and each subsequent cycle, during week 3 of Cycle 2 and every subsequent alternate cycle.

Eligibility
Key inclusion criteria
Patients with any histologically confirmed relapsed or refractory advanced haematologic malignancies for which no effective standard therapies are available. These patients must have progressed following at least one prior treatment regimen. There must be evidence of measurable disease.

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant or lactating women, uncontrolled intercurrent illness, history of other malignancy within 2 years of study entry (excluding treated nonmelanotic skin cancer and in-situ carcinoma), known CNS involvement unless previously treated and well controlled for a period of >=3 months and does not require the use of steroids.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1385 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment postcode(s) [1] 7246 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 287725 0
Government body
Name [1] 287725 0
National Health and Medical Research Council
Address [1] 287725 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 287725 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
St Andrew's Place
East Melbourne, Vic, 3002
Country
Australia
Secondary sponsor category [1] 286455 0
None
Name [1] 286455 0
Address [1] 286455 0
Country [1] 286455 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289684 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 289684 0
Ethics Committee Secretariat
Peter MacCallum Cancer Centre
Level 4, 10 St Andrews Place
East Melbourne, VIC 3002
Ethics committee country [1] 289684 0
Australia
Date submitted for ethics approval [1] 289684 0
Approval date [1] 289684 0
24/01/2013
Ethics approval number [1] 289684 0
12/79

Summary
Brief summary
The study is evaluating the maximum tolerated dose (MTD) by understanding the safety profile during incremental dosage escalation.
Who is it for?
You may be eligible to join this study if you are aged over 18 years with any histologically confirmed relapsed or refractory advanced haematologic malignancies for which no effective standard therapies are available, and have progressed following at least one prior treatment regimen. As every blood cancer patient has a unique disease and treatment history, it is highly suggested that you discuss the trial with your haematologist or oncologist who can also contact Peter Mac to determine whether this trial may be suitable for you.

Trial details
Participants in this study will receive CX-5461, an RNA polymerase I inhibitor. CX-5461 will be administered by intravenous infusion over 1 hour every 21 days. Seven dose levels are planned: 25 mg/m2, 50 mg/m2, 100 mg/m2, 170 mg/m2, 250 mg/m2, 330 mg/m2 and 450 mg/m2 per dose. Patients will be assigned to a dose level in the order of study entry.
Participants will be required to undergo various assessment tests including blood, imaging, laboratory and physical assessment tests.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41910 0
A/Prof Simon Harrison
Address 41910 0
Division of Cancer Medicine
Peter MacCallum Cancer Centre
East Melbourne 3002
Country 41910 0
Australia
Phone 41910 0
+61-3-96561700
Fax 41910 0
Email 41910 0
Simon.Harrison@petermac.org
Contact person for public queries
Name 41911 0
Ms CX-5461 Trial Manager
Address 41911 0
Peter MacCallum Cancer Centre
Centre for Biostatistics & Clinical Trials
East Melbourne 3002
Country 41911 0
Australia
Phone 41911 0
+61-3-96561084
Fax 41911 0
Email 41911 0
ribosome@petermac.org
Contact person for scientific queries
Name 41912 0
A/Prof Simon Harrison
Address 41912 0
Division of Cancer Medicine
Peter MacCallum Cancer Centre
East Melbourne 3002
Country 41912 0
Australia
Phone 41912 0
+61-3-96561700
Fax 41912 0
Email 41912 0
Simon.Harrison@petermac.org

No information has been provided regarding IPD availability
Summary results
No Results