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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03505528




Registration number
NCT03505528
Ethics application status
Date submitted
4/03/2018
Date registered
12/04/2018
Date last updated
12/04/2018

Titles & IDs
Public title
An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer
Scientific title
A Phase Ib Safety and Pharmacokinetics (PK)/ Pharmacodynamics (PD) Study to Determine the Dosage of Abraxane in Combination With Phenelzine Sulfate in Metastatic or Inoperable Locally Advanced Breast Cancer
Secondary ID [1] 0 0
EpiAxis 001-0716
Universal Trial Number (UTN)
Trial acronym
Epi-PRIMED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nanoparticle albumin-bound paclitaxel
Treatment: Drugs - Phenelzine Sulfate

Experimental: Cohort Group - There are five patient cohort groups. Each will receive a progressively higher starting dose of phenelzine sulfate, consecutively. Cohort A will start at 15mg/day and will be increased to 30mg/d by week 2 and further increased to 45mg/d for week 3, which will be maintained throughout the study. Cohort B will start at 45mg/d and will be held constant throughout the Study. Similarly, Cohort C, D & E will start at 60, 75 and 90mg/d, respectively, and will also be held on this dose throughout the study. The decision to escalate the dose for the next cohort will be made on the basis of the number of dose limiting toxicity (DLT) events observed during the first 8 weeks in the preceding cohort group. In addition, all cohort groups will receive a constant dose of Abraxane at 100mg/m2.


Treatment: Drugs: Nanoparticle albumin-bound paclitaxel
Abraxane is administered intravenous at a constant dose of 100mg/m2

Treatment: Drugs: Phenelzine Sulfate
Nardil is administered orally from a starting dose of 15mg/d to a maximum of 90mg/d

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Limiting Toxicity (DLT) events - The number of DLT events for nanoparticle albumin-bound paclitaxel and phenelzine sulfate combined, with the following events assessed using the NCI's CTCAE v4.3 toxicity criteria:
Grade 3 Febrile neutropenia;
Grade =2 peripheral neuropathy;
Any Grade 3 non-haematological toxicity except alopecia; nausea, vomiting, or diarrhoea for 72 hrs due to inadequate use of prophylaxis;
Grade 3 fatigue for > 7 days;
Non-hematologic Grade 3 or 4 laboratory AE that do not return to baseline or to Grade 1 within 7 days;
Grade 3 thrombocytopenia with signs of significant bleeding or platelet count Grade 4;
Blood bilirubin (total) Grade =3 for 72 hrs, AST or ALT Grade 3 for >7 consecutive days, AST or ALT Grade 4;
Persistent Grade 3 hypertension for >7 days & not responding to antihypertensive therapy or Grade 4 hypertension;
An inability to administer treatment (with >7 day delay) during Cycle 1 and Cycle 2 for toxicity reason; &
Any other treatment emergent SAE.
Timepoint [1] 0 0
Assessed throughout the first 56 days
Secondary outcome [1] 0 0
Abraxane Cmax - To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
Timepoint [1] 0 0
Cmax will be assessed on two separate occasions. The first is at day 1 and is for the effect of nanoparticle albumin-bound paclitaxel alone. The second is at day 57 and is for the combined effect with phenelzine sulfate.
Secondary outcome [2] 0 0
Abraxane Tmax - To assess the time after infusion of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate to achieve peak maximum plasma concentration (minutes).
Timepoint [2] 0 0
Tmax will be assessed on two separate occasions. The first is at day 1 and is for the effect of nanoparticle albumin-bound paclitaxel alone. The second is at day 57 and is for the combined effect with phenelzine sulfate.
Secondary outcome [3] 0 0
Abraxane Half-life - To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
Timepoint [3] 0 0
Half-life will be assessed on two separate occasions. The first is at day 1 and is for the effect of nanoparticle albumin-bound paclitaxel alone. The second is at day 57 and is for the combined effect with phenelzine sulfate.
Secondary outcome [4] 0 0
Abraxane AUC - To assess the area under nanoparticle albumin-bound paclitaxel concentration time curve from 0 to infinity (ng minutes / ml) and when combined with phenelzine sulfate.
Timepoint [4] 0 0
AUC will be assessed on two separate occasions. The first is at day 1 and is for the effect of nanoparticle albumin-bound paclitaxel alone. The second is at day 57 and is for the combined effect with phenelzine sulfate.
Secondary outcome [5] 0 0
Nardil Cmax - To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.
Timepoint [5] 0 0
Cmax will be assessed on day 57.
Secondary outcome [6] 0 0
Nardil Tmax - To assess the time after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel, to achieve peak maximum plasma concentration (minutes).
Timepoint [6] 0 0
Tmax will be assessed on day 57.
Secondary outcome [7] 0 0
Nardil Half-life - To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.
Timepoint [7] 0 0
Half-life will be assessed on day 57.
Secondary outcome [8] 0 0
Nardil AUC - To assess the area under Phenelzine Sulfate concentration time curve from 0 to infinity (ng minutes / ml) when combined with nanoparticle albumin-bound paclitaxel.
Timepoint [8] 0 0
AUC will be assessed on day 57.
Secondary outcome [9] 0 0
Circulating Tumour Cell (CTC) burden - The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.
Timepoint [9] 0 0
CTC burden will assessed be at baseline and again at day 29, 57 and 85, whereas the CSC burden will assessed only at baseline and again at day 85.
Secondary outcome [10] 0 0
PDL1 expressing Circulating Tumour Cell (CTC) burden - The PDL1 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
Timepoint [10] 0 0
The PDL1 CTC expression burden will be assessed at baseline and again at day 29, 57 and 85, whereas the CSC burden will assessed only at baseline and again at day 85.
Secondary outcome [11] 0 0
HER2 expressing Circulating Tumour Cell (CTC) burden - The HER2 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
Timepoint [11] 0 0
The HER2 CTC expression burden will be assessed at baseline and again at day 29, 57 and 85, whereas the CSC burden will assessed only at baseline and again at day 85.
Secondary outcome [12] 0 0
FFPE Tumour cells burden - The number of tumour cells observed per FFPE slide.
Timepoint [12] 0 0
Then burden will be assessed at baseline and again at day 85.
Secondary outcome [13] 0 0
FFPE Stoma cells burden - The number of stoma cells observed per FFPE slide.
Timepoint [13] 0 0
Then burden will be assessed at baseline and again at day 85.
Secondary outcome [14] 0 0
FFPE Cancer Stem Cells (CSC) burden - The number of CSC observed per FFPE slide.
Timepoint [14] 0 0
Then burden will be assessed at baseline and again at day 85.

Eligibility
Key inclusion criteria
1. Patients who are 18 years or older;

2. Fluent in written and spoken English and in a position to provide written informed
consent to participate;

3. A patient who is in a position to attend a 12-week treatment regimen and end of study
visit;

4. Metastatic Breast Cancer (MBC) or inoperable locally advanced breast cancer diagnosis
based on pre-existing documented histopathology and medical imaging results, either
Triple Negative Metastatic Breast Cancer (TNBC) or not;

5. Women with metastatic breast cancer or inoperable locally advanced breast cancer who
have not received any cytotoxic therapy in the last 3 weeks;

6. Volunteers of child-bearing potential must have a negative serum pregnancy test (serum
beta-human chorionic gonadotropin or ß-hCG) and have agreed to practice an effective,
reliable contraceptive regimen for the duration of this clinical trial, such as an
intrauterine device (IUD) or intrauterine system (IUS) with a failure rate of <1%
stated on the product label or a male partner who is has been sterilised (vasectomy
with documented azoospermia);

7. ECOG Performance Status 0 or 1; and

8. Adequate liver function as evidenced by bilirubin of <1.5 times upper limit of normal
(ULN) and ALT/AST <2 times of ULN. However, AST and ALT of <5 times ULN if liver
metastases are present.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A patient who has been diagnosed as having HER2-positive metastatic breast cancer;

2. A concurrent condition that may limit the decision-making capabilities of the
participant during the informed consent process;

3. A previous positive diagnosis of Human Immunodeficiency Virus (HIV) and/or Hepatitis C
Virus (HCV) and/or Hepatitis B Virus (HBV) infection;

4. Women who are pregnant or lactating;

5. Uncontrolled, untreated intra-cranial metastases. However, controlled intra-cranial
metastases are allowed, i.e. stable patients with more than a month after the
completion of whole brain radiotherapy and not currently on steroids or
anticonvulsants;

6. Current use of monoamine oxidase inhibitors (MOAI) or use of dextromethorphan

7. Current use of CNS depressants such as selective serotonin re-uptake inhibitors as
well as specific medication for pain management including pethidine, tramadol,
dextromethorphan, fentanyl and/or methadone. This includes the concurrent use of any
serotoninergic agents or buspirone hydrochloride during the week preceding phenelzine
sulfate administration, the active study treatment phase and the washout period at the
end of study. Serotoninergic drugs may include but are not limited to the following:
dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram and
venlafaxine;

8. Previous use of nanoparticle albumin-bound paclitaxel;

9. Known allergy to phenelzine sulfate or similar MOAI; and

10. Known or suspected history of alcohol abuse;

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
ACT,NSW
Recruitment hospital [1] 0 0
Canberra Region Cancer Centre - Canberra
Recruitment hospital [2] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment postcode(s) [1] 0 0
260 - Canberra
Recruitment postcode(s) [2] 0 0
2500 - Wollongong

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EpiAxis Therapeutics
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Canberra Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Southern Medical Day Care Centre
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase 1b study will determine the safety and efficacy of combined treatment of Abraxane
and phenelzine sulfate (Nardil) for metastatic or locally advanced breast cancer.

Participants may be eligible to join this study if they are aged 18 years or above and have
been diagnosed with metastatic breast cancer or inoperable locally advanced breast cancer.

All participants will receive a combination of intravenous Abraxane and an oral dose of
phenelzine sulfate. Abraxane will be administered weekly for the first 3 weeks of a 4-week
cycle for 3 consecutive cycles. Phenelzine sulfate will be taken daily for the duration of
the 3 cycles. Five patient cohort groups will receive a progressively increasing dose of
phenelzine sulfate. Safety and efficacy will be assessed weekly over the 3 cycles of
treatment.

Although both drugs have been used in clinical care for more than a decade, they have not
been intentionally combined together in a cancer therapy setting. This means that the
combined effect of these two drugs has not been documented. This is being addressed in this
study.
Trial website
https://clinicaltrials.gov/show/NCT03505528
Trial related presentations / publications
Boulding T, McCuaig RD, Tan A, Hardy K, Wu F, Dunn J, Kalimutho M, Sutton CR, Forwood JK, Bert AG, Goodall GJ, Malik L, Yip D, Dahlstrom JE, Zafar A, Khanna KK, Rao S. LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer. Sci Rep. 2018 Jan 8;8(1):73. doi: 10.1038/s41598-017-17913-x.
Public notes

Contacts
Principal investigator
Name 0 0
Desmond Yip, MBBS
Address 0 0
ACT Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jeremy S Chrisp, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 421 012 268
Fax 0 0
Email 0 0
j.chrisp@epiaxistherapeutics.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable