This study is a phase I trial. Primary objective is to evaluate the safety of combined radiotherapy with Panitumumab in bladder preservation in invasive bladder cancer. Secondary objectives are to investigate the efficacy of combined radiotherapy…
ID
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Acute Toxicity rate during radiotherapy with Panitumumab treatment (defined in
protocol section 4.4)
Secondary outcome
Secondary endpoints
Complete response rate at 3 months
Local control rate at 6, 12, and 18 months, and at 2 years
Bladder preservation rate
Any grade 3 or 4 adverse event during and within one month after completion
of therapy
Exploratory endpoints
% EGFR expression
RAS mutational status
Response rate in correlation with EGFR and RAS status
Response rate in relation to treatment path
Background summary
There is renewed interest to explore new organ preserving strategies for
invasive bladder cancer. Our goal is to develop an effective treatment strategy
for bladder preservation combing radiotherapy with EGFR targeting after
induction chemotherapy. This new bladder preserving strategy should eventually
be tested against cystectomy in a randomized Phase III trial.
Although radiotherapy is an effective bladder preserving treatment modality for
invasive bladder cancer, the results leave substantial room for improvement.
Several studies have evaluated the efficacy of radiotherapy in combination with
chemotherapy. However, current chemo-radiation schedules are quite toxic and
approximately 1/3 of the patients need a salvage cystectomy as a result of
insufficient response to the treatment. Therefore, new, more effective,
approaches to combined modality treatments of bladder cancer are needed.
As EGFR status seems to be linked to the response to radiotherapy, its
inhibition might enhance the radio-responsiveness of bladder tumors. The first
fully human monoclonal antibody directed against the EGFR receptor Panitumumab
has a high affinity for the EGFR receptor and is characterized by a low
incidence of dose-limiting toxicity. Therefore, the combination of radiotherapy
with Panitumumab is attractive to explore. The purpose of this study is to
evaluate the efficacy and safety of radiotherapy with Panitumumab in bladder
cancer treatment.
Study objective
This study is a phase I trial. Primary objective is to evaluate the safety of
combined radiotherapy with Panitumumab in bladder preservation in invasive
bladder cancer. Secondary objectives are to investigate the efficacy of
combined radiotherapy with Panitumumab in bladder preservation in invasive
bladder cancer.
Study design
Phase I
Intervention
Patients with a T1 to a T4a bladder carcinoma might be eligible for this study
(see protocol section 4.5). Baseline investigations, prior to treatment, will
include history, concomitant drug use, blood analysis, cystoscopy (resections
or biopsies are optional), EGFR and RAS status and a CT of thorax and abdomen.
Patients with N0 disease will have a lymph node dissection (pN0-1 allowed)
followed by 2-4 courses of platinum based chemotherapy, while N1-2 patients
will be treated with 2-4 courses of platinum based chemotherapy followed by a
lymph node dissection (pN0-1 allowed). During chemotherapy treatment patients
will visit their physician at least prior to every course of treatment where
history and concomitant drug use will be taken and blood analysis will be
performed.
After completion of chemotherapeutic treatment and lymph node dissection, and
prior to concomitant radiotherapy and Panitumumab treatment, a CT of thorax and
abdomen will be made and a cystoscopy will be performed Within four weeks
after completion of chemotherapy or lymph node dissection (N+ disease),
radiotherapeutic treatment in combination with Panitumumab treatment will
start. A six-week course of radiotherapy with curative intent will be
administered to the patients (30-33 fractions of 2 Gy). Panitumumab treatment
will be initiated one week before radiotherapy and administered every 2 weeks
during radiotherapy to a total of four courses of 6 mg/kg. Visits during
combined radiotherapy/Panitumumab treatment will be every two weeks with
recording history, concomitant drug use and acute toxicity and blood analysis.
After completion of treatment follow-up will start with visits every three
months with a total of two years. During follow-up visits history, drug use and
toxicity will be recorded and blood analysis will be performed. At 6, 12 , 18
and 24 months after completion of treatment a CT of the pelvis will be made,
while a cystoscopy (resections or biopsies are optional) will be performed
every three months.
Study burden and risks
It is not clear if this treatment is save and efficient. One expects that this
stduy will give a good indication after which one can start a larger trail.
There is always a chance that the patient suffers from adverse events of the
chemotherapy, radiation and/or Panitumumab.
Plesmanlaan 121
1066 CX Amdetrdam
NL
Plesmanlaan 121
1066 CX Amdetrdam
NL
Listed location countries
Age
Inclusion criteria
Signed written informed consent.
Histologically confirmed bladder carcinoma stage (including previous treatment):
T2 N0 M0, refusing surgery and not eligible for brachytherapy
T3-4a N0 M0
T1-4a pN1 M0: with no evidence of lymphnode disease as assessed by CT-scan and pN1
before neoadjuvant chemotherapy as assessed by lymphadenectomy. CR or PR following
neoadjuvant chemotherapy as assessed by CT-scan.
T1-4a N1-2 M0 with evidence of lymphnode disease prior to chemotherapy as assessed by CT
scan and pN0-1 after neoadjuvant chemotherapy as assessed by lymphadenectomy.
Karnofsky performance of * 70 prior to chemotherapy and prior to combined
Panitumumab/radiotherapy treatment.
Hematopoietic function: Neutrophils >= 1.5 x 109/L, platelets >= 100 x 109/L, leucocytes>
3,000/mm3 and hemoglobin >= 9 g/dL.
Hepatic function: Total bilirubin <= 1.5 times the upper normal limit (UNL), ASAT <= 2.5 x UNL and
ALAT <= 2.5 x UNL.
Renal function: Creatinin clearance >= 50 mL/min (calculated clearance).
Metabolic function: Magnesium >= lower limit of normal and Calcium >= lower limit of normal.
Adequate follow-up possibilities for at least two years.
Exclusion criteria
Evidence of M+ (all patients will undergo a pelvic lymphadenectomy prior to chemoradiation).
Prior chemotherapy or radiotherapy to the pelvis.
Prior treatment with anti EGFr and/or anti VEGF treatment.
Previous malignancy except skin carcinoma (basal cell and squamous cell carcinoma).
Candidate for brachytherapy.
No adequate bladder function (functional capacity < 100 cc, frequency > 1/h).
Clinically significant cardiovascular disease (including myocardial infarction, unstable angina,
symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) * 1 year before
enrollment/randomization.
History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of
interstitial lung disease on baseline chest CT scan.
Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the
end of treatment.
Subject (male or female) is not willing to use highly effective methods of contraception (per
institutional standard) during treatment and for 6 months (male or female) after the end of
treatment.
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-018246-38-NL |
| CCMO | NL31148.031.10 |