An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer (Epi-PRIMED)

November 12, 2019 updated by: EpiAxis Therapeutics

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia, 260
        • Canberra Region Cancer Centre
    • New South Wales
      • Sydney, New South Wales, Australia, 2170
        • Liverpool Cancer Therapy Centre
      • Wollongong, New South Wales, Australia, 2500
        • Southern Medical Day Care Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Nanoparticle albumin-bound paclitaxel
Abraxane is administered intravenous at a constant dose of 100mg/m2
Other Names:
  • Abraxane
Drug: Phenelzine Sulfate
Nardil is administered orally from a starting dose of 15mg/d to a maximum of 90mg/d
Other Names:
  • Nardil

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose-Limiting Toxicity (DLT) events
Time Frame: Assessed throughout the first 56 days

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.
Assessed throughout the first 56 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Abraxane Cmax
Time Frame: 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.
To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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.
Abraxane Tmax
Time Frame: 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.
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).
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.
Abraxane Half-life
Time Frame: 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.
To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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.
Abraxane AUC
Time Frame: 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.
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.
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.
Nardil Cmax
Time Frame: Cmax will be assessed on day 57.
To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.
Cmax will be assessed on day 57.
Nardil Tmax
Time Frame: Tmax will be assessed on day 57.
To assess the time after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel, to achieve peak maximum plasma concentration (minutes).
Tmax will be assessed on day 57.
Nardil Half-life
Time Frame: Half-life will be assessed on day 57.
To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.
Half-life will be assessed on day 57.
Nardil AUC
Time Frame: AUC will be assessed on day 57.
To assess the area under Phenelzine Sulfate concentration time curve from 0 to infinity (ng minutes / ml) when combined with nanoparticle albumin-bound paclitaxel.
AUC will be assessed on day 57.
Circulating Tumour Cell (CTC) burden
Time Frame: 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.
The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.
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.
PDL1 expressing Circulating Tumour Cell (CTC) burden
Time Frame: 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.
The PDL1 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
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.
HER2 expressing Circulating Tumour Cell (CTC) burden
Time Frame: 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.
The HER2 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.
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.
FFPE Tumour cells burden
Time Frame: Then burden will be assessed at baseline and again at day 85.
The number of tumour cells observed per FFPE slide.
Then burden will be assessed at baseline and again at day 85.
FFPE Stoma cells burden
Time Frame: Then burden will be assessed at baseline and again at day 85.
The number of stoma cells observed per FFPE slide.
Then burden will be assessed at baseline and again at day 85.
FFPE Cancer Stem Cells (CSC) burden
Time Frame: Then burden will be assessed at baseline and again at day 85.
The number of CSC observed per FFPE slide.
Then burden will be assessed at baseline and again at day 85.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
EpiAxis Therapeutics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Canberra Hospital
Southern Medical Day Care Centre
Liverpool Cancer Therapy Centre

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Desmond Yip, MBBS, ACT Health
  • Principal Investigator: Laeeq Malik, MBBS, ACT Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EpiAxis 001-0716

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

It is the sponsors intention to publish the aggregated study results after the completion of the study.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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