Primary:To establish a recommended phase II dose of the PARP-inhibitor olaparib in combination with hyperthermia in a) patients with recurrent HNC in previously irradiated area and in b) patients with primary irresectable or local recurrent bladder…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is toxicity graded according to the International
Common Toxicity Criteria (CTC), version 4.0.
Secondary outcome
The response rate of olaparib in combination with hyperthermia in patients with
previously irradiated recurrent carcinoma of the head and neck or in patients
with primary irresectable or recurrent bladder cancer unfit for or who
progressed after platinum-based chemotherapy.
HRD induced by hyperthermia in vivo as measured by degradation of the BRCA2
protein or decreased formation of RAD51 foci.
Background summary
In patients with recurrent squamous cell carcinoma of the head and neck as in
patients with primary irresectable or local recurrent bladder cancer major
problems, such as pain (often neuralgic) and severe bleeding may occur, which
are often difficult to control and result in substantial morbidity and poor
quality of life. Few treatment options are available for these patients, also
because of their frail conditions.
Hyperthermia transiently induces HRD in recurrent squamous cell carcinoma of
the head and neck or in primary irresectable or local recurrent bladder cancer
leading to impaired DSB repair, which sensitizes these cancer cells to
treatment with PARP-inhibitors.
We therefore hypothesize that hyperthermia (inducing transient HRD) combined
with a PARP-inhibitor (inducing DSB) in patients with recurrent squamous cell
carcinoma of the head and neck or local recurrent bladder cancer will result in
tumor cell apoptosis, thereby leading to clinical response and palliation.
Study objective
Primary:To establish a recommended phase II dose of the PARP-inhibitor olaparib
in combination with hyperthermia in a) patients with recurrent HNC in
previously irradiated area and in b) patients with primary irresectable or
local recurrent bladder cancer using the maximum tolerated dose (MTD).
Study design
Phase 1 dose-escalation trial
Intervention
Five hyperthermia treatment combined with olaparib twice daily
Study burden and risks
During study treatment (5 weeks) and two weeks thereafter patients have to
visit the clinic, are being seen by the medical oncologist. During these visits
two tubes of blood are taken. When approved by the medical oncologist and
hyperthermia physician hyperthermia takes place. During 4,5 weeks olaparib is
described in different doses in different cohort. No toxicity is to be expected
from hyperthermia or olaparib during a short period of use is being expected,
but no data are known about the combination. As local recurrence often needs
palliation, benefit from treatment may result in relief of symptoms.
Groene Hilledijk 301
Rotterdam 3075EA
NL
Groene Hilledijk 301
Rotterdam 3075EA
NL
Listed location countries
Age
Inclusion criteria
• Recurrent squamous cell carcinoma of the head and neck in previously irradiated area or primary irresectable stage T4 or a local recurrent bladder cancer (urothelial carcinoma or squamous cell carcinoma) in patients unfit for or who progressed after platinum-based chemotherapy and for whom no other treatments are available.
• Age > 18 years
• Performance status WHO 0-1
• Life expectancy of at least 3 months
Exclusion criteria
Curative treatment options available
• Treatment according to guideline available
• Contra-indications for hyperthermia, i.e. patients with a pacemaker or metal implant in the heated area of > 2 cm , multiple sclerosis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003450-40-NL |
| CCMO | NL54543.078.15 |
| OMON | NL-OMON28959 |