A Phase 1 interventional study of Nanoparticle albumin-bound paclitaxel and Phenelzine Sulfate in Metastatic Breast Cancer, sponsored by EpiAxis Therapeutics. Completed at 3 sites in Australia. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-11-13.
Sponsored by EpiAxis Therapeutics · Phase 1, Interventional, and Treatment
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.
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.
12,815 studies on the registry are indexed under Breast Neoplasms; 2,920 are open to participants now.
This study's enrollment of 8 is below the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.
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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 · Drug: Phenelzine Sulfate
Abraxane is administered intravenous at a constant dose of 100mg/m2
Also known as: Abraxane
Nardil is administered orally from a starting dose of 15mg/d to a maximum of 90mg/d
Also known as: Nardil
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.
Time frame: Assessed throughout the first 56 days
Abraxane Cmax
To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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.
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).
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.
Abraxane Half-life
To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.
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.
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.
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.
Nardil Cmax
To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.
Time frame: Cmax will be assessed on day 57.
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).
Time frame: Tmax will be assessed on day 57.
Nardil Half-life
To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.
Time frame: Half-life will be assessed on day 57.
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.
Time frame: AUC will be assessed on day 57.
Circulating Tumour Cell (CTC) burden
The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.
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.
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.
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.
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.
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.
FFPE Tumour cells burden
The number of tumour cells observed per FFPE slide.
Time frame: Then burden will be assessed at baseline and again at day 85.
FFPE Stoma cells burden
The number of stoma cells observed per FFPE slide.
Time frame: Then burden will be assessed at baseline and again at day 85.
FFPE Cancer Stem Cells (CSC) burden
The number of CSC observed per FFPE slide.
Time frame: Then burden will be assessed at baseline and again at day 85.
Plan to share: No — It is the sponsors intention to publish the aggregated study results after the completion of the study.
Ran from Aug 2017 to primary completion in Oct 2019, 26 months.
Of 306 industry-sponsored phase 1 interventional studies under Breast Neoplasms, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 57. This study's 26 months is below that.
Counting every sponsor, half of 645 studies reached it within 45 months; a quarter within 25 and three quarters within 66.
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This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Albumin-Bound Paclitaxel · Phenelzine