Clinical Trial Results:
A Phase II, Open-label, Multicenter Study of PM060184 in Patients with Advanced Colorectal Cancer after Standard Treatment
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Summary
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EudraCT number |
2017-000257-39 |
Trial protocol |
ES |
Global end of trial date |
11 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Oct 2020
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First version publication date |
31 Oct 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PM60184-B-002-17
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03427268 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pharma Mar, S.A.
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Sponsor organisation address |
Avenida de los Reyes, 1 Polígono Industrial "La Mina", Colmenar Viejo, Madrid, Spain, 28770
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Public contact |
Clinical Developtment, Department of PharmaMar´s Oncology, Business Unit., Pharmamar, S.A., 34 91846 60 00, clinicaltrials@pharmamar.com
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Scientific contact |
Clinical Developtment, Department of PharmaMar´s Oncology, Business Unit., Pharmamar, S.A., 34 91846 60 00, clinicaltrials@pharmamar.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Aug 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Feb 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Feb 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of PM060184 in terms of progression-free survival at 12 weeks (PFS3) in patients with advanced colorectal carcinoma (CRC) after standard therapy.
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Protection of trial subjects |
The study was in compliance with ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local
requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
Primary antiemetic prophylaxis was compulsory prior to all PM060184 administrations. Standard treatment, according to American Society of Clinical Oncology (ASCO) guidelines, was administered: • 5-HT3 antagonists (ondansetron 8 mg or equivalent). • Steroids (dexamethasone 8 mg or equivalent). Both oral and i.v. formulations were allowed, following the local institutional standards. If necessary, additional and/or extended antiemetic treatment could be considered in accordance with ASCO guidelines | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jan 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 31
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Country: Number of subjects enrolled |
Canada: 1
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Worldwide total number of subjects |
32
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EEA total number of subjects |
31
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
The first informed consent was signed on 16 January 2018 and the first study treatment administration was on 8 February 2018. The cutoff date for the results was 11 February 2019 (date of last follow-up). | ||||||||||||||||||
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Pre-assignment
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Screening details |
signed CI;Age ≥ 18 years;Histologically-citologically documented adenocarcinoma of colon or rectum that had progressed to the last prior treatment before inclusion;Measurable disease according to RECIST v.1.1;Previous treatment in any setting with fluoropyrimidine, oxaliplatin and irinotecan in any combination;No more than 2 previous therapies | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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PM060184 | ||||||||||||||||||
Arm description |
PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
PM060184
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
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Baseline characteristics reporting groups
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Reporting group title |
Overall period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PM060184
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Reporting group description |
PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point). | ||
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End point title |
Progression-free survival rate at three months [1] | ||||||||
End point description |
Progression-free survival rate at 12 weeks (PFS3), defined as the rate estimate of the percentage of patients who are alive and progression-free at 12 weeks (~3 months) after the first treatment administration.
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End point type |
Primary
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End point timeframe |
Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 3 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The exact binomial estimator and its 95% confidence interval (CI) were used for the primary endpoint (PFS3) |
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| Notes [2] - 2 patients were never treated 1 treated patient not receive 2 administrations over 2 cycles |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
Events 15 (51.7%)
999, not reached
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End point type |
Secondary
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End point timeframe |
From the first day of treatment to the date of death or last contact
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| Notes [3] - 2 patients were never treated 1 treated patient not receive 2 administrations over 2 cycles |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival | ||||||||
End point description |
Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation
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End point type |
Secondary
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End point timeframe |
Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation
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| Notes [4] - 2 patients were never treated 1 treated patient not receive 2 administrations over 2 cycles |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival at 3 months | ||||||||
End point description |
Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation
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End point type |
Secondary
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End point timeframe |
Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 3 months
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| Notes [5] - 2 patients were never treated 1 treated patient not receive 2 administrations over 2 cycles |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Response Rate | ||||||||||||
End point description |
Overall Response Rate defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.1.
PD, disease progression; SD, stable disease; RECIST, Response Evaluation Criteria in Solid Tumors
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End point type |
Secondary
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End point timeframe |
Overall period
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| Notes [6] - 2 patients were never treated 1 treated patient not receive 2 administrations over 2 cycles |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Overall period
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
PM060184
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Reporting group description |
PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 Jul 2017 |
The main objective of this amendment was to change the infusion time of PM060184 from 1 minute to 30 minutes. This was decided following the analysis of preliminary data from the phase II trial PM60184-B-001-15 in hormone receptor-positive, HER2-negative, advanced breast cancer patients, which evaluated short infusion times (one and five minutes) to simplify PM060184 administration. Preliminary safety data from this trial suggest that the overall toxicity profile of PM060184 administered at shorter infusion times (one minute and five minutes) was similar to that observed in 104 patients treated with single-agent PM060184 at different doses during phase I trials. However, it seems that the higher maximum plasma concentration (Cmax) of shorter infusion times was associated with an increased incidence of adverse events at the dose of 9.3 mg/m2. In addition, results from the phase I trial PM60184-A-002a-10, which evaluated the same schedule but at an infusion of 10 minutes, showed that at the recommended dose (RD) of 9.3 mg/m2 five patients had Day 8 infusion omissions, but in only one case the omission was due to drug-related toxicity (grade 2 neutropenia). Thus, the relative dose intensity was 91.3%.
Furthermore, due to its limited solubility, PM060184 must be administered in a very low volume by means of a syringe pump. This device´s performance is highly affected by the system’s pressure, which in turn depends on the duration of the infusion. Thus, the longer the infusion, the fewer chances of device malfunction. Besides, longer infusion times are more convenient for reliable characterization of pharmacokinetic (PK) parameters, especially maximum plasma concentration (Cmax), since these parameters are not affected by variability at the collection window around the end of infusion as much as in shorter infusions. In accordance with these considerations, the infusion time of PM060184 was changed to 30 minutes and the reconstitution guidelines were updated. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
