The primary objective of the study is to evaluate additional safety of RAD001 in patients with MRCC who are intolerant of or whose disease has progressed despite any available prior VEGF receptor tyrosine kinaseinhibitor therapy.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Grade 3/4 adverse events and serious adverse events will be captured
Secondary outcome
Tumor response and progression will be assessed using RECIST Criteria.Tumor
assessments of measurable (CT scan/MRI) disease/lesions will be performed at
screening and repeated every 3 months for the first year and then every 6
months thereafter, and at discontinuation of the study drug. Lesion size and
measurements will not be collected; however, the Investigator*s best overall
response will be captured.
After the administration of the last dose of RAD001 or RAD001 becomes
commercially available, no further AEs/SAEs or survival data will be collected
after the required 28 day safety interval.
Background summary
RAD001 (everolimus, an mTOR inhibitor) is an oral derivative of rapamycin. and
was approved in 2003 in Europe (trade name: Certican®) for the prevention of
organ rejection in patients with renal and cardiac transplantation. RAD001 is
also being investigated as an anticancer agent based on its potential to act
directly on the tumor cells by inhibiting tumor cell growth and proliferation
and indirectly by inhibiting angiogenesis via potent inhibition of tumor cell
HIF-1 activity and VEGF production and VEGF-induced proliferation of
endothelial cells. At weekly and daily schedules and at various doses explored
RAD001 has been generally well tolerated. The most frequent adverse events
(rash, mucositis, fatigue and headache) associated with RAD001 have been
manageable. Non-infectious pneumonitis has been reported with mTOR inhibitors
but is commonly low-grade and reversible with RAD001.
Novartis has filed an NDA in MRCC in EU and US as of June 2008. There are no
other agents with demonstrated efficacy in this disease setting. Based on the
results of the Phase III pivotal registration study, this expanded access
protocol is designed to fulfill an unmet medical need by providing RAD001 to
patients who are without satisfactory
treatment alternatives.
Study objective
The primary objective of the study is to evaluate additional safety of RAD001
in patients with MRCC who are intolerant of or whose disease has progressed
despite any available prior VEGF receptor tyrosine kinase
inhibitor therapy.
Study design
This is an open-label, multi-center protocol designed to evaluate additional
safety of RAD001 and to make RAD001 available to patients with MRCC who are
intolerant of or whose disease has progressed on any available VEGF receptor
tyrosine kinase inhibitor therapy. No other agents have demonstrated efficacy
in this disease setting. Safety data will fulfill
international regulatory requirements.
All patients will be screened for inclusion and exclusion criteria within five
weeks prior to the first dose of RAD001. See Table 7-1 of the protocol for a
description of the screening evaluations required.
Baseline evaluations will be performed within two weeks of the first dose of
RAD001. See Table 7-1 of the protocol for a description of the baseline
evaluations required.
Subsequently, patients will be asked to visit the clinic monthly thereafter.
For purposes of this study each cycle will be 28 days and study drug will be
administered continuously.
Intervention
A daily, oral dose of 10 mg RAD001 will be administered continuously from
start until either progression of disease, unacceptable toxicity, death,
discontinuation from study from any other reason, or until the drug becomes
commercially available for MRCC in each participating country or until 15 Juni
2010, whichever occurs first.
Study burden and risks
Apart from a pregnancy test, if applicable, and a request to use barrier
contraceptives, if applicable, extra invasive procedures outside the routine
care for this patient group are not requested. The additional risks associated
with participation in this study, in view of the general condition of the
target population and the lack of alternative treatment options, are considered
to be low.
Postbus 241
6800 LZ Arnhem
Nederland
Postbus 241
6800 LZ Arnhem
Nederland
Listed location countries
Age
Inclusion criteria
• Age >= 18 years old.
• Patients with histologically or cytologically confirmed metastatic renal cell
carcinoma.
• Patients who are intolerant of or have progression on or after stopping
treatment with any available VEGF receptor tyrosine kinase inhibitor
therapy.
• Prior vaccine therapy or treatment with cytokines (i.e., IL-2, Interferon)
and/or VEGF-ligand inhibitors (i.e., bevacizumab) is permitted.
• Patients with measurable or non-measurable disease by RECIST criteria.
• Patients with history of another distinguishable malignancy (such as nonmelanoma skin cancer, or low grade lymphoma, or CLL, or well
controlled low grade prostate cancer), which are neither life threatening
nor require chemotherapy or radiation.
• Patients with history of brain metastasis who are neurologically stable
following definitive radiation or surgery and do not require corticosteroids.
• Patients with a Karnofsky Performance Status >=70%.
• Patients with adequate bone marrow function defined as ANC >= 1.5 x
109/L, Platelets >= 100 x 109/L, Hgb >9 g/dL.
• Patients with adequate liver function defined as serum bilirubin <= 1.5 x
ULN, ALT and AST <= 2.5x ULN. Patients with known liver metastases
who have an AST and ALT <= 5x ULN.
• Patients with adequate renal function defined as serum creatinine <= 2 x
ULN.
• Women of childbearing potential must have had a negative serum or
urine pregnancy test within 14 days prior to the administration of study
drug.
• Patients must give written informed consent according to local guidelines.
Exclusion criteria
• Patients receiving chemotherapy, immunotherapy, radio-therapy or any
other investigational agent (including pazopanib) within 4 weeks of study
entry, or sunitinib and/or sorafenib within 1 week of the first dose of
RAD001.
• Patients who have previously received RAD001 or other mTOR inhibitors.
• Patients with a known hypersensitivity to RAD001 or other rapamycin
analogs (sirolimus, temsirolimus), or to its excipients.
• Patients receiving systemic treatment with corticosteroids or another
immunosuppressive agent. Patients may receive low dose treatment of
corticosteroids with a maximum dose of 20 mg prednisone or 10 mg
dexamethasone per day, if they are being given for disorders such as
rheumatoid arthritis, asthma, or adrenal insufficiency. Topical or inhaled
corticosteroids are permitted.
• Patients with an active bleeding diathesis.
• Patients who have undergone major surgery within 4 weeks prior to
starting study drug (e.g., intra-thoracic, intra-abdominal, or intra-pelvic),
open biopsy, or significant traumatic injury, or who have not recovered
from the side effects of any of the above.
• Patients with any severe and/or uncontrolled medical conditions such as
unstable angina pectoris, symptomatic congestive heart failure,
myocardial infarction <= 6 months, serious uncontrolled cardiac
arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe
infection, cirrhosis, chronic or persistent active hepatitis or severely
impaired lung function.
• Uncontrolled diabetes (fasting glucose > 2x ULN)
• Female patients who are pregnant or breast feeding, or adults of
reproductive potential who are not using effective birth control methods.
If barrier contraceptives are used, they must be continued throughout the
study by both sexes.
• Patients unwilling to or unable to comply with the protocol.
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 | EUCTR2007-005460-28-NL |
| ClinicalTrials.gov | NCT00655252 |
| CCMO | NL24639.058.08 |