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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03505528
Registration number
NCT03505528
Ethics application status
Date submitted
4/03/2018
Date registered
23/04/2018
Titles & IDs
Public title
An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer
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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
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Secondary ID [1]
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EpiAxis 001-0716
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Universal Trial Number (UTN)
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Trial acronym
Epi-PRIMED
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer
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Condition category
Condition code
Cancer
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Breast
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Dose-Limiting Toxicity (DLT) events
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Assessment method [1]
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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.
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Timepoint [1]
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Assessed throughout the first 56 days
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Secondary outcome [1]
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Abraxane Cmax
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Assessment method [1]
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To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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Timepoint [1]
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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.
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Secondary outcome [2]
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Abraxane Tmax
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Assessment method [2]
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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).
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Timepoint [2]
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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.
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Secondary outcome [3]
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Abraxane Half-life
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Assessment method [3]
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To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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Timepoint [3]
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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.
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Secondary outcome [4]
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Abraxane AUC
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Assessment method [4]
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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.
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Timepoint [4]
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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.
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Secondary outcome [5]
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Nardil Cmax
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Assessment method [5]
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To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.
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Timepoint [5]
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Cmax will be assessed on day 57.
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Secondary outcome [6]
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Nardil Tmax
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Assessment method [6]
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To assess the time after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel, to achieve peak maximum plasma concentration (minutes).
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Timepoint [6]
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Tmax will be assessed on day 57.
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Secondary outcome [7]
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Nardil Half-life
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Assessment method [7]
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To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.
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Timepoint [7]
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Half-life will be assessed on day 57.
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Secondary outcome [8]
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Nardil AUC
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Assessment method [8]
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To assess the area under Phenelzine Sulfate concentration time curve from 0 to infinity (ng minutes / ml) when combined with nanoparticle albumin-bound paclitaxel.
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Timepoint [8]
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AUC will be assessed on day 57.
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Secondary outcome [9]
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Circulating Tumour Cell (CTC) burden
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Assessment method [9]
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The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.
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Timepoint [9]
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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.
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Secondary outcome [10]
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PDL1 expressing Circulating Tumour Cell (CTC) burden
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Assessment method [10]
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The PDL1 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
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Timepoint [10]
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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.
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Secondary outcome [11]
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HER2 expressing Circulating Tumour Cell (CTC) burden
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Assessment method [11]
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The HER2 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
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Timepoint [11]
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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.
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Secondary outcome [12]
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FFPE Tumour cells burden
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Assessment method [12]
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The number of tumour cells observed per FFPE slide.
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Timepoint [12]
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Then burden will be assessed at baseline and again at day 85.
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Secondary outcome [13]
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FFPE Stoma cells burden
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Assessment method [13]
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The number of stoma cells observed per FFPE slide.
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Timepoint [13]
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Then burden will be assessed at baseline and again at day 85.
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Secondary outcome [14]
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FFPE Cancer Stem Cells (CSC) burden
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Assessment method [14]
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The number of CSC observed per FFPE slide.
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Timepoint [14]
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Then burden will be assessed at baseline and again at day 85.
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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.
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Minimum age
18
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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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;
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Study design
Purpose of the study
Treatment
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Allocation to intervention
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
17/08/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/10/2019
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Sample size
Target
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Accrual to date
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Final
8
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Recruitment in Australia
Recruitment state(s)
ACT,NSW
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Recruitment hospital [1]
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Canberra Region Cancer Centre - Canberra
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Recruitment hospital [2]
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Liverpool Cancer Therapy Centre - Sydney
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Recruitment hospital [3]
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Southern Medical Day Care Centre - Wollongong
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Recruitment postcode(s) [1]
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260 - Canberra
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Recruitment postcode(s) [2]
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2170 - Sydney
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Recruitment postcode(s) [3]
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2500 - Wollongong
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
EpiAxis Therapeutics
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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The Canberra Hospital
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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Southern Medical Day Care Centre
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Address [2]
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Country [2]
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Other collaborator category [3]
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Government body
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Name [3]
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Liverpool Cancer Therapy Centre
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Address [3]
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Country [3]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT03505528
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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. Erratum In: Sci Rep. 2019 Dec 5;9(1):18771. doi: 10.1038/s41598-019-55020-1. Tan AHY, Tu W, McCuaig R, Hardy K, Donovan T, Tsimbalyuk S, Forwood JK, Rao S. Lysine-Specific Histone Demethylase 1A Regulates Macrophage Polarization and Checkpoint Molecules in the Tumor Microenvironment of Triple-Negative Breast Cancer. Front Immunol. 2019 Jun 12;10:1351. doi: 10.3389/fimmu.2019.01351. eCollection 2019. Prasanna T, Malik L, McCuaig RD, Tu WJ, Wu F, Lim PS, Tan AHY, Dahlstrom JE, Clingan P, Moylan E, Chrisp J, Fuller D, Rao S, Yip D. A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED). Front Oncol. 2022 Jun 3;12:862427. doi: 10.3389/fonc.2022.862427. eCollection 2022.
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Public notes
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Contacts
Principal investigator
Name
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Desmond Yip, MBBS
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Address
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ACT Health
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
It is the sponsors intention to publish the aggregated study results after the completion of the study.
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03505528