A phase II trial whose main objective is to investigate the response rate of the primary tumor following pretreatment with sunitinib
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main end point of this study is any objective response in the primary tumor
according to RECIST criteria .
Secondary outcome
Cancer specific survival and morbidity, overall response at metastatic sites
and duration of metastatic response will be assessed. (Duration of overall
survival; duration of hospital stay; percentage of withdrawal from nephrectomy
due to sunitinib-related reduction of performance; response at metastatic
sites; progression to irresectability of the primary tumor during initial
treatment).
Immunomonitoring in the peripheral blood at different time intervals and the
primary tumor after nephrectomy.
Imaging with CT and dynamic MRI scan prior to treatment with sunitinib and
prior to nephrectomy to identify potential response criteria other than RECIST
in association with histopathology.
Background summary
All present trials with sunitinib involving primary metastatic RCC included
patients after nephrectomy. That design was chosen because the preferred
treatment of primary metastatic RCC patients was nephrectomy first followed by
therapy with interferon alpha to treat the remaining metastases. As a result no
data exist about the response of primary tumors to sunitinib. This is of
importance, because cytoreductive nephrectomy may have a different role in
medical treatment with tyrosine-kinase inhibitors than with interferon alpha.
However, it is known that an impressive number of patients have partial
responses of their metastases after sunitinib using RECIST criteria. In a
recent phase III trial that was 31 % for sunitinib versus 6 % for interferon
alpha. It may therefore be that - potentially - the primary tumors would have
had an equally high response rate if they would not have been removed prior to
treatment.
Study objective
A phase II trial whose main objective is to investigate the response rate of
the primary tumor following pretreatment with sunitinib
Study design
The study is designed as a phase II trial of initial sunitinib followed by
nephrectomy in primary metastatic renal cell carcinoma with the primary tumor
in situ.
This study is designed to detect a 25 % objective response rate in the primary
tumor according to RECIST criteria with an alpha of 0.05 and a power of 80 %
using a two-stage minimax design developed by Simon.
First, 22 patients will be treated and if at most 1 response is observed in the
primary tumor, the study will be stopped for insufficient activity on the
primary tumor. If at least 2 responses are obtained, 18 additional patients
will be included to a total of 40 patients. If at least 8 primary tumors of
these patients respond the treatment will be declared to have sufficient
activity on the primary tumor (alpha=0.05 and 80% power if the response is 25%
or more). Otherwise the treatment will be declared not sufficiently active on
the primary tumor.
Intervention
After patients have expressed that they are willing to take part in the trial,
but before registration, those without a histological diagnosis of clear-cell
renal cell cancer will undergo 3 transcutaneous tru-cut biopsies of the primary
tumor or alternatively a metastatic lesion after local anesthesia with 1 %
lidocaine has been applied.Eligible patients will start with sunitinib at a
continuous dose of 50 mg/day for 2 cycles of each 4 weeks with 2 weeks off
treatment. Patients who deteriorate during treatment or have to withdraw from
sunitinib because of side effects will be excluded from the study treatment and
offered second-line treatment (investigators choice) after recovery, followed
at three-monthly intervals. At completion of the 2nd treatment cycle of 4 weeks
tumor assessments are made and patients admitted for surgery maximally 1 week
later. All patients will undergo delayed transabdominal tumornephrectomy with
resection of all encompassable metastases, including those patients with
progressive metastases, unless rapid progression leads to a deterioration of
performance of WHO 2 or worse. After a 3 weeks rest period postoperative tumor
assessments are performed and the medication will be continued as 4/2 regimen
until progression.
Study burden and risks
The accepted treatment for primary metastatic renal cell carcinoma is a
multimodality approach of surgery and medical treatment. In Europe sunitinib
has been registered as first line treatment. The best timing of nephrectomy,
surgery either before medical treatment or following medical treatment, is not
known.
Therefore, the proposed treatment in this trial does not deviate from the
accepted concept of a combination of medical and surgical treatment. The only
additional burden is drawing blood for immunological examination and the two
dynamic MRI scans.
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
1. Histologically confirmed metastatic renal cell cancer of clear-cell subtype with a resectable asymptomatic primary in situ. Unless the diagnosis of a clear-cell subtype has been established after histological examination of a resected metastatic lesion, all patients need to undergo a transcutaneous tru-cut needle biopsy of the primary tumor.
2. Extensive metastatic disease which is defined as 3 or more non-resectable metastases in case of 1 metastatic site, using the RECIST criteria, or 2 or more metastatic sites.
3. Age: 18 to 65 years
4. Life expectancy > 3 months
5. WHO performance status 0 or 1
6. Written informed consent obtained from the patient after having been informed about the objectives of the study and the medication used.
7. Blood counts: Leucocytes > 3.0 x 109/l, platelets > 100 x 109/l, hemoglobin > 6.0 mmol/l.
8. Serum bilirubin, ASAT, ALAT and creatinin within 1.5 times of upper limit of reference values of laboratory.
9. No prior systemic treatment with biological response modifiers, tyrosine-kinase inhibitors, monoclonal antibodies or chemotherapy. Patients who receive local radiotherapy for bone lesions can be included.
10. An intermediate MSKCC risk profile.
11. In women of child-bearing age anticonception is required.
12. Patients should be able to drink 2 to 3 liters per day.
Exclusion criteria
1. Symptomatic primary necessitating nephrectomy. For definition see Inclusion criteria of the protocol.
2. Irresectable primary tumor
3. Patients in whom complete surgical remission can be achieved by removing metastatic sites at nephrectomy or by delayed surgery.
4. Previous nephrectomy
5. Low metastatic burden (2 or less non-resectable metastases at 1 metastatic site)
6. Metastatic RCC to the bone only. Bone metastases are considered truly non measurable.
7. Current cardiovascular disease, hematopoetic, pulmonary, hepatic or renal dysfunction or WHO performance status > 1.
8. Previous immunotherapy, therapy with tyrosine-kinase inhibitors, monoclonal antibodies or chemotherapy.
9. Presence of autoimmune disease, HIV and hepatitis.
10. Corticosteroid and/ or other immunosuppressive therapies.
11. Prior malignancies. In case of NED the period should be > 5 years.
12. Central nervous system metastases.
13. non-clear cell subtype.
14. Poor or good prognosis according to MSKCC risk assessment.
15. Pregnancy, lactation or no anticonception in women of child-bearing age.
16. Inability to drink at least 2 liters per day.
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 | EUCTR2006-006491-38-NL |
| CCMO | NL15556.031.06 |