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Metastatic Breast CancerPhase 1Epi-PRIMEDNCT03505528

An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer

A Phase 1 study testing Nanoparticle albumin-bound paclitaxel and Phenelzine Sulfate in people with Metastatic Breast Cancer, run by EpiAxis Therapeutics at 3 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Nanoparticle albumin-bound paclitaxel and Phenelzine Sulfate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
3 sitesAustralia
Study dates
17 Aug 2017to 30 Oct 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who are 18 years or older;
  • Fluent in written and spoken English and in a position to provide written informed consent to participate;
  • A patient who is in a position to attend a 12-week treatment regimen and end of study visit;
  • 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;
  • Women with metastatic breast cancer or inoperable locally advanced breast cancer who have not received any cytotoxic therapy in the last 3 weeks;
  • 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);
  • ECOG Performance Status 0 or 1; and
  • 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.

Who cannot join

  • A patient who has been diagnosed as having HER2-positive metastatic breast cancer;
  • A concurrent condition that may limit the decision-making capabilities of the participant during the informed consent process;
  • A previous positive diagnosis of Human Immunodeficiency Virus (HIV) and/or Hepatitis C Virus (HCV) and/or Hepatitis B Virus (HBV) infection;
  • Women who are pregnant or lactating;
  • 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;
  • Current use of monoamine oxidase inhibitors (MOAI) or use of dextromethorphan
Show all 10Show fewer
  • 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;
  • Previous use of nanoparticle albumin-bound paclitaxel;
  • Known allergy to phenelzine sulfate or similar MOAI; and
  • Known or suspected history of alcohol abuse;

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

  • Canberra Region Cancer Centre

    Canberra, Australian Capital Territory, 260

  • Liverpool Cancer Therapy Centre

    Sydney, New South Wales, 2170

  • Southern Medical Day Care Centre

    Wollongong, New South Wales, 2500

Other trials in Australia

About this study

Official 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

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.

Read more

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.

Read the detailed description

Nanoparticle albumin-bound paclitaxel (Abraxane) will be administered intravenously over 3 cycles at a fixed dosage of 100mg/m2 to each study participant. This dose will be administered weekly for the first 3 consecutive weeks, over the 4 week cycle, before commencing the second and third cycles.

In addition to the fixed dose of nanoparticle albumin-bound paclitaxel, all patients will receive a continuous daily oral dose of phenelzine sulfate across all three cycles,

Each of the five patient cohort groups 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.

Phenelzine sulfate compliance will be monitored weekly based on drug tablet returns.

Being tested
Nanoparticle albumin-bound paclitaxel, Phenelzine Sulfate
Keywords
Nanoparticle albumin-bound paclitaxel (Abraxane), Phenelzine Sulfate, Cancer stem cells, epigenetics, LSD1
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nanoparticle albumin-bound paclitaxelDrug

    Also called Abraxane

    Abraxane is administered intravenous at a constant dose of 100mg/m2

  • Phenelzine SulfateDrug

    Also called Nardil

    Nardil is administered orally from a starting dose of 15mg/d to a maximum of 90mg/d

Study groups in NCT03505528
Study groupRoleWhat they receive
Cohort GroupExperimentalThere 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.
Receives: Drug: Nanoparticle albumin-bound paclitaxel; Drug: Phenelzine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Assessed throughout the first 56 days

Secondary outcomes (14)

  1. Abraxane Cmax

    To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.

    Measured: 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.

  2. 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).

    Measured: 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.

  3. Abraxane Half-life

    To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.

    Measured: 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.

  4. 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.

    Measured: 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.

  5. Nardil Cmax

    To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.

    Measured: Cmax will be assessed on day 57.

  6. 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).

    Measured: Tmax will be assessed on day 57.

  7. Nardil Half-life

    To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.

    Measured: Half-life will be assessed on day 57.

  8. 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.

    Measured: AUC will be assessed on day 57.

  9. Circulating Tumour Cell (CTC) burden

    The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.

    Measured: 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.

  10. 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.

    Measured: 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.

  11. 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.

    Measured: 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.

  12. FFPE Tumour cells burden

    The number of tumour cells observed per FFPE slide.

    Measured: Then burden will be assessed at baseline and again at day 85.

  13. FFPE Stoma cells burden

    The number of stoma cells observed per FFPE slide.

    Measured: Then burden will be assessed at baseline and again at day 85.

  14. FFPE Cancer Stem Cells (CSC) burden

    The number of CSC observed per FFPE slide.

    Measured: Then burden will be assessed at baseline and again at day 85.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2018
  2. Study start17 Aug 2017
  3. Primary completion30 Oct 2019
  4. Study completion30 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Intervention model
Sequential
Model description
An open, non-randomised, cumulative cohort group design (across 5 groups) with a target toxicity fraction of 30% and a margin of 10%. This means that a dose will be escalated between groups when the observed toxicity rate is \< 20%, de-escalated when \> 40% and maintained otherwise. The toxicity fraction is the number of participants receiving that dose who experience a DLT.
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03505528
Sponsor's protocol ID
EpiAxis 001-0716
Acronym
Epi-PRIMED
Status last verified
Jul 2019
First submitted
4 Mar 2018
Last updated
13 Nov 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: It is the sponsors intention to publish the aggregated study results after the completion of the study.

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.

    PubMed 29311580

  • 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.

    PubMed 31249575

  • 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.

    PubMed 35719960

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nanoparticle albumin-bound paclitaxel and Phenelzine Sulfate in people with Metastatic Breast Cancer, run by EpiAxis Therapeutics at 3 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-Limiting Toxicity (DLT) events (time frame: Assessed throughout the first 56 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03505528, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.

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