Clinical trial NCT01959438: Sodium Selenite as a Cytotoxic Agent in Advanced Carcinoma
Official title: Sodium Selenite as a Cytotoxic Agent in Advanced Carcinoma. A Phase I and Phase II Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Malignant Tumor
Treatment Resistant Disorders
Tumor Progression
Keywords: Phase I study for safety
Later Phase II study for responses
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Cancerfonden
name: Cancer and Allergy Foundation
name: Cancerföreningen i Stockholm
name: Region Stockholm
First posted: 2013-10-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In vitro studies have demonstrated that sodium selenite in sufficient concentration and during sufficient time have a high tumoricidal capacity. This is found in many human cell types as leukemia cells, mesothelioma and non-small cell lung cancer cells. A minority of cell lines seem to be resistant. The question from a clinical point of view is: Is it possible with respect to toxicity to administer sodium selenite to patients in sufficient dose and during sufficient time to get responses in patients with cancer? We have performed first part of phase-1 study and found MTD of 10.2 mg/m2 if given as 10 daily infusions during 12 days. We have recorded limited anti-tumor effect in this treatment regimen. However, in vitro data suggest that low concentration of continuous exposure for 51 h is much more effective. Now we are planning to continue the phase-I trial with modified protocol.

More specific:

1. Phase I: Find maximal tolerable dose with continuous infusion
2. Phase II: Use MTD and study responses, if any

Detailed description: * Patients: With advanced malignant disease, any kind, in which all standard treatment has been tried, but still progression. In sufficient good performance status (ps 0-2)to get more treatment: first selenite and immediately afterwards chemotherapy (since an additive or synergistic effect from selenite and chemotherapy has been found).
* Treatment: We have performed the initial study with sodium selenite i.v. daily, 10 treatments during 2 weeks. The week after that response evaluation and then chemotherapy. In each patient, his or her first line chemotherapy treatment is given, since in vitro studies indicate that selenite might reverse resistance. In the modified protocol, a 2 days continuous infusion will be performed.
* Toxicity evaluation (main criteria in phase I): Meeting a doctor once a week during selenite treatment and before each chemotherapy treatment and at End of treatment. Meeting a nurse each treatment day during selenite treatment. Blood samples for liver, kidney, blood and thyroid values. Plasma samples for selenite concentration during treatment.
* Response evaluation (to be: main criteria in phase II and studied also in phase I): CT scan just before and after selenite treatment and after chemotherapy. From May 2011 FDG-PET-CT-scan just before and after selenite treatment. Cytokeratin and cytokeratin fragments evaluation.

Eligibility criteria: Inclusion Criteria:

* Advanced malignant tumor disease
* All standard treatments should have been tested, but the disease still progressing.
* In sufficient good performance status to get more treatment
* Informed consent

Exclusion Criteria:

* More than 1 active tumour disease
* Impaired capacity to cooperate
* Serious other disease such as heart or kidney disease that might give extra risk for complications and difficulties to interpret effect of the selenite treatment
* The tumour not possible to evaluate

Primary outcomes:
measure: Maximal tolerable dose (phase I, ongoing)
timeFrame: within three year
Secondary outcomes:
measure: Responses
timeFrame: Two years within the phase I study
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Onkologkliniken, (Dept of Oncology) Södersjukhuset
Study officials:
affiliation: Karolinska University Hospital
name: Ola Brodin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: