Clinical Trial Results:
Safety, pharmacokinetics and efficacy of AXP107-11 in combination with standard gemcitabine (Gemzar®) treatment in patients with locally advanced or metastatic, unresectable, adenocarcinoma of the pancreas, stage III-IV. A prospective, open label, multi-centre, sequential phase Ib/IIa study.
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Summary
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EudraCT number |
2010-019214-25 |
Trial protocol |
SE |
Global end of trial date |
07 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jul 2017
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First version publication date |
27 Jul 2017
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Other versions |
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Summary report(s) |
AXP107-11 Clinical Study Report Synopsis |
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 |
AXP-CT-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01182246 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Axcentua Pharmaceuticals AB
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Sponsor organisation address |
Grev Turegatan 13A, Stockholm, Sweden, SE-114 46
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Public contact |
Anders Berkenstam, Axcentua Pharmaceuticals AB, +46 70 779 58 12, anders.berkenstam@axcentua.com
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Scientific contact |
Anders Berkenstam, Axcentua Pharmaceuticals AB, +46 70 779 58 12, anders.berkenstam@axcentua.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 |
07 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Dec 2014
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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 |
Primary objectives
Phase Ib
The primary objective is to determine the safety profile and MTD of AXP107-11 alone and when given in combination with gemcitabine standard therapy.
Safety will be assessed by occurrence of adverse events, abnormal changes in laboratory parameters, vital signs, ECG and relevant patient withdrawal.
Phase IIa
The primary objective is to assess the effect of a combination therapy of AXP107-11 and gemcitabine on objective response rate defined as the percentage of patients who showed complete response (CR) or partial response (PR).
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Protection of trial subjects |
The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki that are consistent with International Conference on Harmonisation/Good Clinical Practice and applicable regulatory requirements. Informed consent was obtained from all patients prior to initiation of the study.
During Phase Ib, patients were hospitalised during the first 24 hours on Day -13 and Day 1 for close safety monitoring and PK sampling. The safety evaluation was based on clinical signs and symptoms and laboratory safety assessments (including complete blood count).
A study patient was withdrawn from the study treatment if, in the opinion of the Investigator, it was medically necessary (e.g. unacceptable AE), or if it was the expressed wish of the patient.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Nov 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Sweden: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
16
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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) |
12
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
This trial was performed at 2 clinical sites in Stockholm, Sweden. Consenting patients were screened for eligibility within 2 weeks prior to start of AXP107-11 treatment. Eligible patients were included in consecutive order into the initial dose-escalation part of the study (phase Ib) or directly into the maintenance part (phase IIa). | ||||||||||||||
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Pre-assignment
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Screening details |
Male and female patients ≥ 18 years of age who were chemotherapy naive with histologically confirmed, unresectable, locally advanced or metastatic pancreatic cancer stage III-IV with a Karnofsky Performance Status (KPS) score ≥ 70 and life expectancy of more than 3 months were considered for participation. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (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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AXP107-11 alone and when given in combination with gemcitabine | ||||||||||||||
Arm description |
Phase Ib: Four cohorts, of 3 to 7 patients each, were treated with escalating dose levels of AXP107-11 alone (2 weeks) and in combination with gemcitabine (1 week). All patients included in the dose escalation phase were evaluated for the presence of dose limiting toxicity (DLT). Patients who did not fulfill any discontinuation criteria and who were not in disease progression were continued into the maintenance phase of the study (i.e. Phase IIa). All phase Ib patients were progressed to Phase IIa. No new patients enrolled directly into Phase IIa. Phase IIa: Patients started treatment with AXP107-11 alone for 2 weeks, followed by combination treatment with gemcitabine. Study treatment with the combination treatment was continued until disease progression, severe toxicity, patient withdrawal or a maximum of 6 months, whichever came first. Follow-up: All patients had a follow-up evaluation 28 ± 7 days after the last administration of study medication, if possible. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
AXP107-11 (4',5,7-trihydroxyisoflavone-Na-dihydrate)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Phase Ib:
In the dose escalation part of the study (phase Ib), AXP107-11 was administered once daily on the first treatment day (morning) to get a 24-hour PK profile, followed by twice daily administrations continuously throughout the treatment period. Patients were hospitalised for 24 hours on Day -13 and Day 1 for close safety monitoring and PK sampling. The patients within each dose level started treatment sequentially with at least 24 hrs between each patient, following a safety evaluation of the previous patient(s). AXP107-11 dosage was escalated as follows; 400 mg daily, 800 mg daily, 1200 mg daily and 1600 mg daily.
Phase IIa:
All 16 patients from Phase Ib continued in a modified maintenance phase (Phase IIa) in which they were treated with the dose of AXP107-11 that they received during Phase Ib; dose-escalation phase. Phase IIa patients started treatment with AXP107-11 alone for 2 weeks, followed by combination
treatment with gemcitabine.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study (overall period)
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Reporting group description |
Male and female (≥ 18 years) chemotherapy naive patients with histologically confirmed, unresectable, locally advanced or metastatic pancreatic cancer stage III-IV treated with AXP107-11 alone and in combination with Gemcitabine (Gemzar®). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AXP107-11 alone and when given in combination with gemcitabine
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Reporting group description |
Phase Ib: Four cohorts, of 3 to 7 patients each, were treated with escalating dose levels of AXP107-11 alone (2 weeks) and in combination with gemcitabine (1 week). All patients included in the dose escalation phase were evaluated for the presence of dose limiting toxicity (DLT). Patients who did not fulfill any discontinuation criteria and who were not in disease progression were continued into the maintenance phase of the study (i.e. Phase IIa). All phase Ib patients were progressed to Phase IIa. No new patients enrolled directly into Phase IIa. Phase IIa: Patients started treatment with AXP107-11 alone for 2 weeks, followed by combination treatment with gemcitabine. Study treatment with the combination treatment was continued until disease progression, severe toxicity, patient withdrawal or a maximum of 6 months, whichever came first. Follow-up: All patients had a follow-up evaluation 28 ± 7 days after the last administration of study medication, if possible. | ||
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End point title |
Karnofsky Performance Status scale (KPS) [1] | ||||||||||||||
End point description |
KPS is a standard way of measuring the ability of cancer patients to perform ordinary tasks. The KPS
scores range from 0 to 100. A higher score means the patient is better and able to carry out daily activities.
100-80 = Able to carry on normal activity and to work; no special care needed.
50-70 = Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.
40 -0 = Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
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End point type |
Primary
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End point timeframe |
Karnofsky Performance Status scale (KPS) was assessed at screening, baseline (Day -13) and thereafter weekly during the study period, including follow-up.
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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: No formal statistical and analytical plan was written. Descriptive data are summarised and/or listed as considered appropriate. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Tumor response (RECIST) [2] | ||||||||||||||||||
End point description |
Evaluation of target and non-target lesions for:
- Complete Response (CR)
- Partial Resposnse (PR)
- Progressive Disease (PD)
- Stable Disease (SD)
- non CR/non-PD
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End point type |
Primary
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End point timeframe |
Tumour response was evaluated at the following time
points: Visit 8 (Day 1), Visit 14 (Day 29), Visit 17 (Day 50), Visit 25 (week 4 of cycle 3), Visit 33 (week 4
of cycle 5), as a confirmation of CR or PR after 4 weeks, at the follow-up.
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| Notes [2] - 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: No formal statistical and analytical plan was written. Descriptive data are summarised and/or listed as considered appropriate. |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
AEs were to be noted during the single agent AXP107-11 treatment period (Days -13 and -6) and during cycle 1 (Days 1, 8, 15, 22, 29, 36, and 43) and during the remaining cycles on Days 1, 8, 15 and at follow-up.
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Adverse event reporting additional description |
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Male and female (≥ 18 years) chemotherapy naive patients with histologically confirmed, unresectable, locally advanced or metastatic pancreatic cancer stage III-IV treated with AXP107-11 alone and in combination with Gemcitabine (Gemzar®). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: AEs were not summarised in tables by system organ class and preferred term. AEs were not coded according to Medical Dictionary for Regulatory Activities (MedDRA) |
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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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08 Jul 2011 |
Clinical Study Protocol Amendment 1 Final dated 2011-05-10
Changes in the conduct of the study. |
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17 Apr 2012 |
Clinical Study Protocol Amendment 2 Final dated 2012-02-20 Final
Changes in the conduct of the study, blood sampling (PK analyses). |
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28 May 2013 |
Clinical Study Protocol Amendment 3 dated 2013-03-18
Changes in conduct of the study, changes in patient information. |
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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 | |||
