Clinical Trial Results:
PHASE II STUDY OF LUTETIUM-177 LABELED CHIMERIC MONOCLONAL ANTIBODY cG250 (177Lu-DOTA-cG250) TREATMENT IN PATIENTS WITH ADVANCED RENAL CANCER
Summary
|
|
EudraCT number |
2008-004548-35 |
Trial protocol |
NL |
Global end of trial date |
03 Aug 2015
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
23 Aug 2024
|
First version publication date |
23 Aug 2024
|
Other versions |
|
Summary report(s) |
Synopsis acc ICH e3 177Lutetium_cG250 in RCC Phase II clinical trial |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
15081982
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02002312 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Radboud University Medical Centre
|
||
Sponsor organisation address |
Geert Groote plein Zuid 10, Nijmegen, Nijmegen, Netherlands, 6525GA
|
||
Public contact |
RadboudUMC, RadboudUMC, +31 243613735, secretariaat.uro@radboudumc.nl
|
||
Scientific contact |
RadboudUMC, RadboudUMC, +31 243613735, secretariaat.uro@radboudumc.nl
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
03 Aug 2015
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
03 Aug 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
03 Aug 2015
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To determine the clinical efficacy of multiple doses of 177Lutetium-girentuximab (177Lu-cG250) at MTD in patients with advanced renal cancer using RECIST criteria.
|
||
Protection of trial subjects |
Patients who fulfilled the selection criteria:
Inclusion Criteria:
- Patients with proven advanced and progressive renal cell carcinoma of the clear cell type
- At least one evaluable lesion less than 5 cm
- Performance status: Karnofsky > 70 %
- Laboratory values obtained less than 14 days prior to registration:
- White blood cells (WBC) > 3.5 x 109/l
- Platelet count > 100 x 109/l
- Hemoglobin > 6 mmol/l
- Total bilirubin < 2 x upper limit of normal (ULN)
- ASAT, ALAT < 3 x ULN (< 5 x ULN if liver metastases present)
- Serum creatinine < 2 x ULN
- Negative pregnancy test for women of child¬bearing potential (urine or serum)
- Age over 18 years
- Ability to provide written informed consent
Exclusion Criteria:
- Known metastases to the brain
- Untreated hypercalcemia
- Metastatic disease limited to the bone
- Pre-exposure to murine/chimeric antibody
- Chemotherapy, external beam radiation, immunotherapy or angiogenesis inhibitors within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed, when unirradiated, evaluable lesions elsewhere are present.
- Cardiac disease with New York Heart Association classification of III or IV
- Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception
- Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator will significantly affect patients’ clinical status
- Life expectancy shorter than 6 months.
Patients were controlled as follows:
- Wk 1: screening and injection 111In-cG250 (day 1) and 2 scans (day 2-4 and 5-7)
- Wk 2: injection 177Lu-cG250 and subsequent hospital admission for 1 night only
- Wk 3 until 8: Weekly visit UMCN for blood draw and physical exam.
- W 3 - 6: during fulminant hematological toxicity increased checks laboratory values
- Wk 12: CT-scan and Wk 13: blood draw
|
||
Background therapy |
not applicable | ||
Evidence for comparator |
not applicable | ||
Actual start date of recruitment |
01 Aug 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 14
|
||
Worldwide total number of subjects |
14
|
||
EEA total number of subjects |
14
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
6
|
||
From 65 to 84 years |
8
|
||
85 years and over |
0
|
|
|||||||||||||||
Recruitment
|
|||||||||||||||
Recruitment details |
In total, 16 adult patients with metastatic clear cell renal cell carcinoma (ccRCC) were enrolled between August 2011 and April 2014 to participate in this Study if metastasis showed targeting of diagnostic imaging. | ||||||||||||||
Pre-assignment
|
|||||||||||||||
Screening details |
After screening 2 patients were excluded from the study because known ccRCC lesions did not show any targeting at diagnostic imaging postinjection of indium 111 (111In)–girentuximab. 14 patients who showed targeting at scans postinjection of indium 111 (111In)–girentuximab were eligible for treatment with 177Lutetium-girentuximab. | ||||||||||||||
Period 1
|
|||||||||||||||
Period 1 title |
Cycle 1
|
||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
No blinding was chosen in this first pilot study of treatment with 177Lutetium-girentuximab.
|
||||||||||||||
Arms
|
|||||||||||||||
Arm title
|
Cycle 1 | ||||||||||||||
Arm description |
In Cycle 1, 14 patients started treatment with 177Lutetium-cG250 at a dose level of 2405 MBq/m2. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
cG250
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
LUTETIUM-177 LABELED CHIMERIC MONOCLONAL ANTIBODY cG250; 177Lu-DOTA-cG250; 177Lutetium-girentuximab
|
||||||||||||||
Pharmaceutical forms |
Solution for injection in administration system
|
||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||
Dosage and administration details |
In Cycle 1, 14 patients received 177Lutetium cG2502 at a dose of 2405 MBq/m2.
|
||||||||||||||
|
|||||||||||||||
Period 2
|
|||||||||||||||
Period 2 title |
Evaluation results Cycle 1
|
||||||||||||||
Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Arms
|
|||||||||||||||
Arm title
|
Eligible to start in Cycle 2 | ||||||||||||||
Arm description |
To evaluate if patients were eligible for treatment in Cycle 2 | ||||||||||||||
Arm type |
No intervention | ||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
||||||||||||||
|
|||||||||||||||
Period 3
|
|||||||||||||||
Period 3 title |
Cycle 2
|
||||||||||||||
Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
In Cycle 2, 6 patients started treatment with 177Lutetium-cG250 at a dose level of 1805 MBq/m2.
|
||||||||||||||
Arms
|
|||||||||||||||
Arm title
|
Cycle 2 | ||||||||||||||
Arm description |
In Cycle 2, 6 patients started treatment with 177Lutetium-cG250 at a dose level of 1805 MBq/m2. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
cG250
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
LUTETIUM-177 LABELED CHIMERIC MONOCLONAL ANTIBODY cG250; 177Lu-DOTA-cG250; 177Lutetium-girentuximab
|
||||||||||||||
Pharmaceutical forms |
Solution for injection in administration system
|
||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||
Dosage and administration details |
In Cycle 2, 14 patients received 177Lutetium cG2502 at a dose of 1805 MBq/m2.
|
||||||||||||||
|
|||||||||||||||
Period 4
|
|||||||||||||||
Period 4 title |
Evaluation results Cycle 2
|
||||||||||||||
Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Arms
|
|||||||||||||||
Arm title
|
Eligible to start in Cycle 3 | ||||||||||||||
Arm description |
To evaluate if patients were eligible for treatment in Cycle 3 | ||||||||||||||
Arm type |
No intervention | ||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||
Reporting group title |
Cycle 1
|
||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, 14 patients started treatment with 177Lutetium-cG250 at a dose level of 2405 MBq/m2. | ||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Cycle 1
|
||
Reporting group description |
In Cycle 1, 14 patients started treatment with 177Lutetium-cG250 at a dose level of 2405 MBq/m2. | ||
Reporting group title |
Eligible to start in Cycle 2
|
||
Reporting group description |
To evaluate if patients were eligible for treatment in Cycle 2 | ||
Reporting group title |
Cycle 2
|
||
Reporting group description |
In Cycle 2, 6 patients started treatment with 177Lutetium-cG250 at a dose level of 1805 MBq/m2. | ||
Reporting group title |
Eligible to start in Cycle 3
|
||
Reporting group description |
To evaluate if patients were eligible for treatment in Cycle 3 |
|
|||||||||||||||||||
End point title |
Clinical response 3 months after treatment [1] | ||||||||||||||||||
End point description |
|||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Clinical response was evaluated 3 months after treatment by using CT scanning and evaluation according to RECIST v1.1.
|
||||||||||||||||||
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: A Simon two-stage minimax design was used to calculate the no. of patients needed to reach a desirable response rate (RR) defined as at least Stable Disease (RECIST v1.1). If RR >0.25 after the first cycle of treatment in the first 6 patients after 3 months, 14 patients had to be included. Desirable RR was set at 0.65 with alpha of 0.05 and beta of 0.10. Response was defined as at least SD on RECIST v1.1 evaluation after 3 months. After 6 patients RR was 0.5 so 14 patients were included. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Toxicity of treatment 12 weeks after treatment | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Patients were monitored at least once a week for 12 weeks for hematological toxicity (using Common Toxicity Criteria for Adverse Events v.3.0)
|
|||||||||||||||
|
||||||||||||||||
Notes [2] - 14 patients received Cycle 1 [3] - 6 patients received Cycle 2 |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were evaluated the whole study period.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events were evaluated using the Common Toxicity Criteria V3.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Per Protocol reporting group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All 14 patients who received treatment according to the protocol were in the intention to treat reporting group for adverse event reporting. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/26706103 |