Patients with stage III or IV cancer in whom first and second line treatment have been given but who have tumours that are still progressing, giving symptomes. The patients must be in a fairly good condition (performance status 0-2) and considered to manage the treatment, sodiumselenite and chemotherapy as out-patients. The study treatment might be considered as a last rescue in this group of patients with an expected median survival of only a few months.
Conditions
Interventions
Trade Name: Intro-Selen iv
Product Name: Intro-Selen iv
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Introselen iv
Other descriptive name: Sodium selenite
Concentration un
Sponsors
Huvud- hals- lung- och hudcancer, Tema Cancer Karolinska Universitetssjukhuset
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Advanced malignant disease of any kind. 2. Histologically or cytologically verified tumor. 3. Progressing tumor in spite of earlier treatment with established drug treatment for respective tumor. (It is the patient´s responsible doctor, who decides that). 4. All stages, but according to point 3, mostly stage IV patients will be considered for inclusion. Patients with brain metastases might be considered if they have been treated with irradiation or surgery and are free from symptoms of the brain metastase. 5. Performance status 0, 1 and 2. 6. More than 18 years of age. 7. Radiation therapy or chemotherapy should not have been given for at least 3 weeks before start of selenite. 8. The patient must accept to give blood and urine samples for routine and researhc purposes. It is desirable to take tumor biopsies twice (before and after selenite treatment). If biopsy taking is associated with a high risk for serious complications, this will not be done. 9. Spoken and written informed consent. 10. The patient must accept that data are checked by a person outsied the study (monitor). 11. The patient and the PAL (patient responsible doctor) must accept that the study treatment and the follow-ups within the study are performed at the HHH section of Radiumhemmet, Karolinska University Hospital. A note to the patient´s record should be performed by the PAL that 1) established drug treatment has been given and 2) that the 12 week´s treatment within the SECAR study shall be undertaken at the HHH section of Radiumhemmet. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Dysfunction of heart, kidney (cystatin C >1.60, if on limit Pt-eGFR 50) or other organs that might give a considerable increased risk for patient safety. 2. Impaired ability to cooperate. 3. The tumour not possible to evaluate. 4. Two or more concurrent malignancies. If no signs of one of them during the last 3 years, the patient can be included. 5. Ongoing treatment with antidepressive drugs. 6. Obstacle in the pharynx giving risk for aspiration pneumonia if vomiting. 7.Brain metastases giving symptoms and also symptomless brain metastases localised in the pons region. CT-scan of the brain, not older that 6 weeks before start of treatment must be free from metastases in the pons region. Patients with treated brain metastases (irradiation or surgery) and free from symptoms can be included. 8. Patients with HIV/AIDA or hepatitis B/C with respect to increased risks for nurses and laboratory people working with blood samples.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The trial has two parts. In the first, phase I part, the objective is to find the MTD of sodiumselenite. The patients will receive a 2 (or 3) day continuous infusion of sodium-selenite and after that a response evaluation will be performed. If not progression, the patient will receive 2 more 2 day infusions. A new response evaluation is now performed. After that (or immediately if progression) the patient will be treated with 3-4 courses with the kind of chemotherapy that has been used as first line treatment. Then the last response evaluation is done. In the second, the phase II part, the objective is to find out if sodium-selenite given at MTD dose has an anti-tumor effect, either alone or after the chemotherapy treatment. Both in the phase I and phase II studies we will aim to get tumor samples before and immediately after the selenite treatment. Thus the primary endpoint in the phase I study is MTD and safety and in the phase II responses. ;Secondary Objective: In the phase I study:Responses, degree and duration. Survival. Dose/toxicity correlation In the phase II study: Toxicity, type, degree, duration, safety. Dose /effect correlation In both parts of the study: Pharmacokinetics of sodium-selenite. Metabolism of selenite, expression of selenoproteins. Search for predictive markers Relation, if any, between the level of thioredoxinreductase and antitumoural effect Impact of selenite on interleukines and other immunological factors. ;Primary end point(s): In the first, phase I part: Primary endpoint: MTD (safety). The patients will receive 2 and 3 days, respectively continuous infusion with sodiumselenite. A PET-CT scan will be performed just before and after the first treatment. If no tumor progression 2 more continuous infusions will be given. A CT scan if taken . After that (or if progression after the first infusion) chemotherapy, 3 -4 courses will be given and a CT scan taken. After that an End of treatment meeting with the doctor (inv | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): This will take longer, and analysis will be performed during half a year after the stop of inclusion.;Timepoint(s) of evaluation of this end point: These results will take longer, since measurement of selenite is performed a few times during each study and the same is true about speciation of selenite metabolites. Calculation of pharmacokinetics will be performed when all data on selenium in plasma have arrived. Similarily it will take extra time to obtain data on necrosis and apoptosis of selenium biopsies and chemosensitivity of ex vivo studies of chemosensitivity. These data, however, have no impact on the duration of inclusion time , only on time to publication. | — |
Countries
Sweden
Contacts
Public ContactClara Lenneby-Helleday
Huvud- hals- lung- och hudcancer, Tema Cancer Karolinska University Hospital
Outcome results
None listed