|- candidate number||6702|
|- NTR Number||NTR2103|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-nov-2009|
|- Secondary IDs||2007/056 METc UMCG Groningen|
|- Public Title||Beeldvorming met radioactief TRM-1 bij patienten met solide kanker in gevorderd stadium, die worden behandeld met gemcitabine, cisplatin en TRM-1.|
|- Scientific Title||Imaging with radiolabeled TRM-1 in patients with solid malignancies who are treated with gemcitabine, cisplatin and TRM-1.|
|- hypothesis||To visualize the tumor and to study normal tissue biodistribution and pharmacokinetics of radiolabeled TRM-1.
|- Healt Condition(s) or Problem(s) studied||Advanced solid tumors, Advanced solid malignancies|
|- Inclusion criteria||1. Histologically or cytologically confirmed advanced solid malignancy in a subject who has relapsed after or is refractory to standard therapy, for whom no standard therapy exists, or for whom the combination of gemcitabine and cisplatin is considered an appropriate standard treatment;|
2. Measurable (according to the RECIST Criteria) or evaluable disease;
3. Adequate hematologic function and bone marrow reserve:
A. Absolute neutrophil count (ANC) ¡Ý 1.5 x 109/L;
B. Platelet (PLT) count ¡Ý 100 x 109/L;
C. Hemoglobin ¡Ý 5.6 mmol/L.
4. Adequate hepatic and renal function:
A. ASAT and ALAT ¡Ü 2.5 fold upper limit of normal (ULN);
B. Bilirubin ¡Ü 1.25 fold ULN;
C. Creatinine ¡Ü 1.25 fold ULN or calculated creatinine clearance ¡Ý 60 mL/min.
5. Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale;
6. Life expectancy of at least 3 months;
7. Age of 18 or older;
8. Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures.
|- Exclusion criteria||1. Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduces the probability of assessing clinical effect;|
2. Cytotoxic agent, hormonal therapy, or radiation therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to day 1, cycle 1; investigational agent within 4 weeks prior to day 1, cycle 1;
3. Monoclonal antibody (including investigational monoclonal antibodies) within 3 weeks (murine or chimeric) or 8 weeks (human or humanized) prior to day 1, cycle 1;
4. Systemic steroids within 1 week prior to day 1, cycle 1 except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease;
5. Major surgery within 4 weeks prior to day 1, cycle 1;
6. Persistent grade 2 or greater toxicity (NCI-CTCAE, version 3.0, 12 December 2003) related to prior therapy (except alopecia);
7. Any grade 2 or greater neuropathy;
8. Hearing loss requiring the use of a hearing aid;
9. History of any infection requiring hospitalization or antibiotics within 2 weeks prior to day 1, cycle 1;
10. Myocardial infarction (MI), cerebrovascular accident (CVA), or ¡Ý Class III congestive heart failure (CHF) according to the New York Heart Association Classification for within 6 months prior to day 1, cycle 1;
11. Known brain metastases unless adequately treated (surgery or radiotherapy), with no evidence of progression and neurologically stable off anticonvulsants and steroids;
12. Known human immunodeficiency virus (HIV) infection;
13. Known chronic or acute viral hepatitis;
14. Pregnant or breast-feeding women. Women with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test at screening. All non-sterile, non-postmenopausal females must agree to use a medically approved method of contraception during the study and for 60 days following the final dose;
15. Males who do not agree to use effective contraception during the study and for a period of 60 days following the final dose.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||22-nov-2007|
|- planned closingdate||1-mrt-2010|
|- Target number of participants||10|
|- Interventions||Patients with advanced solid malignancies, who relapsed or are refractory to standard therapy, for whom no standard therapy exists, or for whom the combination of gemcitabine and cisplatin is considered an appropriate standard treatment. |
These patients are treated with gemcitabine, cisplatin and TRM-1 every 3 weeks. Imaging will be performed directly, and at day 1, 3, and 6 after IV injection of radiolabeled TRM-1 in cycle 1 and 3.
|- Primary outcome||1. To visualize the tumor (imaging);|
2. To study normal tissue biodistribution and pharmacokinetics of radiolabeled TRM-1.
|- Secondary outcome||Safety.|
|- Timepoints||1. Gemcitabine, cisplatin and TRM-1 every 3 weeks IV, up to 6 cycles;|
2. Whole body and SPECT imaging directly, and at day 1, 3, and 6 after IV injection of radiolabeled TRM-1 in cycle 1 and 3.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| C.N.A.M. Oldenhuis|
|- CONTACT for SCIENTIFIC QUERIES||Prof.dr. E.G.E. Vries, de |
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|University Medical Center Groningen (UMCG)|
|- Brief summary||TRM-1 is a monoclonal antibody to TRAIL-R1. In a phase 1b study, the combination of TRM-1 with gemcitabine and cisplatin was safe and well tolerated in patients with solid malignancies. In order to study the biodistribution of TRM-1, the compound was labeled with Indium-111 for gammacamera imaging. Imaging with indium-111 labeled TRM-1 has been successfully tested in mice. In this study we would like to evaluate the pharmacokinetics, biodistribution and tumor uptake of 111In-TRM-1 in 10 patients with solid malignancies. These patients are treated with gemcitabine, cisplatin and TRM-1. TRM-1 scans will be made during treatment cycles one and three. After each tracer injection four TRM-1 scans will be made. Furthermore, blood samples will be obtained and urine will be collected for pharmacokinetic analysis.|
|- Main changes (audit trail)|
|- RECORD||9-nov-2009 - 25-nov-2009|