Clinical Trial Results:
A Phase IIa Exploratory Study of CriPec® docetaxel Monotherapy in Subjects with Platinum Resistant Ovarian Cancer.
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Summary
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EudraCT number |
2018-002117-36 |
Trial protocol |
NL BE GB |
Global end of trial date |
06 Jul 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jan 2021
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First version publication date |
08 Jan 2021
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Other versions |
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Summary report(s) |
SMS-0423_CINOVA_Synopsis final CSR_01Dec2020_signed |
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 |
CT-CL02
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03742713 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
SMS-oncology study number: SMS-0423 | ||
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Sponsors
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Sponsor organisation name |
Cristal Therapeutics
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Sponsor organisation address |
Oxfordlaan 55, Maastricht, Netherlands, 6229 EV
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Public contact |
Rob Hanssen, Cristal Therapeutics, info@cristaltherapeutics.com
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Scientific contact |
Rob Hanssen, Cristal Therapeutics, info@cristaltherapeutics.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 |
01 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Jul 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jul 2020
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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 determine the Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of CriPec® docetaxel monotherapy in subjects with ovarian cancer who are resistant to prior platinum-based therapy.
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Protection of trial subjects |
Corticosteroid pre-medication was administered to prevent skin toxicities.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Oct 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 |
Netherlands: 10
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Country: Number of subjects enrolled |
Belgium: 15
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Worldwide total number of subjects |
25
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EEA total number of subjects |
25
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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) |
11
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
This trial was conducted in 8 centers divided over 3 countries: The Netherlands, Belgium and the United Kingdom. 6 out of 8 centers recruited patients. First patient was included 19Oct2018. Last study visit before database lock was 06Jul2020. | ||||||
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Pre-assignment
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Screening details |
Patients with ovarian and peritoneal cancer resistant to prior platinum-based therapy. Total number of patients was 25 with 25 being part of the safety set population, and 23 being part of the per protocol set. Stage 1: first 13 patients included Stage 2: altered inclusion criteria to match those of hallmark Docetaxel trials | ||||||
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Period 1
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Period 1 title |
Overall trial (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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Received at least one dose CriPec©docetaxel | ||||||
Arm description |
Subjects eligible for the trial received CriPec®docetaxel Q3W at the RP2D of 60 mg/m2. Each treatment cycle consisted of 21 days. On Day 1 of each cycle, a single dose of CriPec®docetaxel was administered IV at a constant rate for ~1 hour. Pre-treatment with dexamethasone 8.0 mg orally was given three times before each CriPec®docetaxel administration (night before, morning and 1 hour before treatment). Stage 1: (N=13) Simon 2-stage design. Stage 2: (N=12). Simon 2-stage design no longer applicable. Maximum allowed treatment lines reduced from 3 to 2 lines, in both cases of which one could have been taxane-based. Life expectancy requirement extended from 12 weeks to 5 months. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
CriPec©docetaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The dose selection for CT-CL02 was based on previous experience from trial CT-CL01, where
the R2PD of 60 mg/m2 with corticosteroid premedication was selected based on the following:
• There was a significant decrease of skin toxicities (all severity grades) comparing 70 mg/m2 to 60 mg/m2 dose level at the Q3W schedule;
• Addition of corticosteroid premedication to the 60 mg/m2/Q3W regimen prevented acute skin reactions. Also, at the 60 mg/m2 dose plus corticosteroids, overall less AEs have been reported;
• The average length of therapy at 60 mg/m2 plus corticosteroids was longer (~5.2 treatment cycles) than without co-medication (~3.2 treatment cycles);
The complete dose of CriPec®docetaxel had to be administered via IV infusion. Start and stop times had to be noted. If the administration was interrupted and subsequently restarted, the start and stop times of the re-administration must have also been noted.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Q3W IV CriPec©docetaxel administration at 60mg/m2, with corticosteroid premedication (three times 8.0 mg oral dexamethasone before each CriPec®docetaxel dose). * Stage 1 (N=13): There was no limit to the number of previous treatment lines, but a maximum of 3 lines of therapy for platinum-resistant disease, of which one could have been taxane-based. Life expectancy required of at least 12 weeks. * Stage 2: Subjects who have received a maximum of 2 prior treatment lines, of which one could have been taxane-based. Life expectancy required of at least 5 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Stage 1
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
There was no limit to the number of previous treatment lines, but a maximum of 3 lines of therapy for platinum-resistant disease, of which one could have been taxane-based. Life expectancy required of at least 12 weeks.
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Subject analysis set title |
Stage 2
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects who have received a maximum of 2 prior treatment lines, of which one could have been taxane-based. Life expectancy required of at least 5 months.
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End points reporting groups
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Reporting group title |
Received at least one dose CriPec©docetaxel
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Reporting group description |
Subjects eligible for the trial received CriPec®docetaxel Q3W at the RP2D of 60 mg/m2. Each treatment cycle consisted of 21 days. On Day 1 of each cycle, a single dose of CriPec®docetaxel was administered IV at a constant rate for ~1 hour. Pre-treatment with dexamethasone 8.0 mg orally was given three times before each CriPec®docetaxel administration (night before, morning and 1 hour before treatment). Stage 1: (N=13) Simon 2-stage design. Stage 2: (N=12). Simon 2-stage design no longer applicable. Maximum allowed treatment lines reduced from 3 to 2 lines, in both cases of which one could have been taxane-based. Life expectancy requirement extended from 12 weeks to 5 months. | ||
Subject analysis set title |
Stage 1
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
There was no limit to the number of previous treatment lines, but a maximum of 3 lines of therapy for platinum-resistant disease, of which one could have been taxane-based. Life expectancy required of at least 12 weeks.
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Subject analysis set title |
Stage 2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who have received a maximum of 2 prior treatment lines, of which one could have been taxane-based. Life expectancy required of at least 5 months.
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End point title |
ORR as assessed by RECISTV1.1 calculated as proportion of subjects who achieved CR or PR [1] | ||||||||||||||||||||||||||||||||
End point description |
ORR as assessed by RECISTV1.1
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End point type |
Primary
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End point timeframe |
At any time point prior to end of trial (when the subject had either discontinued trial treatment or received six cycles of treatment, whichever occurred first).
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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 analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Safety, evaluated by means of physical examinations, body weight, vital signs, ECOG, lab, ECG and AEs | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
For physical examinations, body weight, vital signs lab, and ECG parameters no clear impact on safety could be detected. For an overview of the Adverse Events, please refer to the Adverse Event section of this report.
ECOG changes during the trial to higher grades were generally recorded for higher numbers of subjects in Stage 2 than in Stage 1.
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End point type |
Secondary
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End point timeframe |
Safety parameters were recorded from screening until day 22 of the last cycle (EOT). Both ECOG and vital signs were additionally recorded at the safety follow-up visit 28 days after EOT. SAEs regarded related to IMP were followed until end of study.
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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 |
Subjects were monitored for AEs from screening and during each subject visit until 22 days after last CriPec©docetaxel administration (EOT visit). In addition, ongoing SAEs were assessed at the 28-day FU, regardless of its relationship to the IMP.
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Adverse event reporting additional description |
AEs occurring after EOT and coming to the attention of the Investigator must be recorded only if they are considered (in the opinion of the Investigator) related to CriPec©docetaxel.
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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 |
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Subjects eligible for the trial received CriPec®docetaxel Q3W at the RP2D of 60 mg/m2. Each treatment cycle consisted of 21 days. On Day 1 of each cycle, a single dose of CriPec®docetaxel was administered IV at a constant rate for ~1 hour. Pre-treatment with dexamethasone 8.0 mg orally was given three times before each CriPec®docetaxel administration (night before, morning and 1 hour before treatment). Stage 1: (N=13) Simon 2-stage design. Stage 2: (N=12). Simon 2-stage design no longer applicable. Maximum allowed treatment lines reduced from 3 to 2 lines, in both cases of which one could have been taxane-based. Life expectancy requirement extended from 12 weeks to 5 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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11 Sep 2018 |
Protocol V3.0_25Sep2018 (NL, UK) and V2.0_11Sep2018 (Belgium-specific).
For both UK and BE these protocols were approved under the Initial study approval. For NL it has been an amendment (SA01). The changes compared to V1.0_01Jun2018 include administrative changes and changes as directed by the CA of BE:
-Frequency of pregnancy tests increased for women of childbearing potential
-Further specification of footnotes of the schedule of assessments
-Removal of some biochemistry parameters
-Specification of the moment of EOT
-Specification about SAE FU at safety FU visit |
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28 May 2019 |
Protocol V4.0_20May2019 & Protocol V5.0_24Jun2019 after comments of the CA of NL
The protocol was amended after data review of the first stage of the trial. The following changes were applied in protocol V4.0:
- Modification of inclusion criterion maximum number of treatment lines allowed to match those of landmark docetaxel trials
-Required life expectancy increased from 12 weeks to 5 months
-Therefore no longer a Simon 2-stage study design
-Updated dose modification criteria
-Introduction of possibility to replace subjects under certain conditions
-Change of scan interval changed from: SCR, after 6 weeks and every 12 weeks thereafter, to: SCR, after 9 weeks and every 9 weeks thereafter;
-Updated safety information from previous trials IB V5.0;
-Introduction of slot reservation process prior to subject registration;
-Cap of 2 patients per site for the first 8 included patients to ensure balanced recruitment.
In protocol V5.0, a limit to the number of patients that may be replaced (max. 7) was introduced following comments from the CA in NL. Protocol V5.0 was submitted as a notification to UK and BE to ensure the same protocol version was used in all participating countries.
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17 Mar 2020 |
Investigator's Brochure March2020
-Updated trial status
-Updated reference safety information |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 | |||||||
