To investigate whether hyperthermia induces HR-deficiency in cervical tumors and as a feasibility study, secondly to investigate whether it is possible to detect circulating tumor cells before and after hyperthermia.
ID
Source
Brief title
Condition
- Cervix disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The level of BRCA2 protein as detected by immuno (Western) blotting with
anti-BRCA2 antibody before and after hyperthermia as a measure of homologous
recombination (HR) deficiency. In parallel, part of the pre-hyperthermia
obtained tumor cells will be incubated at 37*C or 41*C in the laboratory, as an
ex vivo control experiment in the same patient.
Secondary outcome
The presence of CTC before and after hyperthermia treatment.
Background summary
Cervical cancer is the third most common type of cancer among women and in
advanced cases and recurrent disease the outcome is poor. Therefore, there is
an urgent need to enhance the effectiveness of current therapies and to develop
new strategies for treating cervical cancer.
Hyperthermia is currently added to radiotherapy in locally advanced cervical
cancer and added to chemotherapy in local recurrent disease. Recently it has
been demonstrated in vitro that mild hyperthermia (41 - 42.5 °C) leads to
degradation of BRCA2. BRCA2 deficiency inhibits homologous recombination (i.e.
HR-deficiency), a DNA repair mechanism. Defective HR-deficiency sensitizes
cells to double-strand break-inducing therapy like platinum derivates,
radiation and poly (ADP-ribose) polymerase (PARP)-1 inhibitors.
Confirmation of these results in human cervical tumor samples will support the
current treatment of chemotherapy or radiotherapy combined with hyperthermia by
gaining insight into the mechanism of action. Furthermore, it will be a useful
model to study the effect of new therapeutic strategies on HR deficiency in
cervical tumors.
In several carcinomas including breast and prostate, enumeration of circulating
tumor cells (CTC) bears prognostic information. In cervical cancer, it is
unknown whether CTC can be detected, and the role of CTC has not been studied.
Study objective
To investigate whether hyperthermia induces HR-deficiency in cervical tumors
and as a feasibility study, secondly to investigate whether it is possible to
detect circulating tumor cells before and after hyperthermia.
Study design
Pilot study.
Study burden and risks
Benefit: This is a pilot study to provide proof of principle of a preclinical
proven concept of in vitro hyperthermia induced HR-deficiency in cervical
tumors and to investigate whether it is possible to identify circulation tumor
cells in locally advanced cervical carcinoma. This will be of no benefit for
the individual patient on the short term. However, once the concept is
confirmed, an intervention trial will be planned, in order to show benefit of
hyperthermia-induced HR-deficiency for future patients.
Risks: The patient will undergo two tumor biopsies and 2 venous blood samples
will be taken. Since the biopsies are small (4 mm only) and patients with
bleeding disorders are excluded, no serious risks are to be expected other than
discomfort and minimal blood loss.
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
• Cervical cancer patients with a routine indication for primary treatment combined with hyperthermia
• Tumor lesions amendable for biopsies
• Age >18 years
• Platelets >100 x 10e9/L
• Written informed consent
Exclusion criteria
• Current therapeutically use of anti-coagulant (coumarin, warfarin, heparin or low molecular weight heparin [LMWH]). LMWH if used for prophylaxis is allowed.
• Any psychological condition potentially hampering compliance with the study protocol.
• Patients who are treated in another institution for radiotherapy, with more than 2 hour travel distance.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49462.078.14 |