Compare Progression Free Survival (PFS) for brivanib versus placebo in subjects with advanced solid tumors with FGF-2 over-expression and who have obtained stable disease after 12 weeks of treatment with brivanib separately for each tumor.
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 outcome measure is Progression*free Survival (PFS) time defined as
the length of time during
and after treatment in which a patient is living with a disease that does not
get worse. In this trial the PFS of
patients with advanced solid tumours who have achieved disease stabilization
after an initial 12*week
treatment with brivanib and are randomized to continue treatment will be
compared to those who are
randomized to receive a placebo. Subjects who did not progress nor die will be
censored at the date of the last tumour measurement.
Secondary outcome
The secondary outcome measures include:
•Objective response rate defined as the percentage of patients whose cancer
shrinks or disappears during
and after treatment based on an established method of imaging and measurement
of tumour lesions.
•Duration of response defined as the length of time between the detection of
tumour size reduction or
disappearance and the recurrence or worsening of the disease.
•Time to response defined as the length of time from the start of study
treatment and the detection of tumour
size reduction or disappearance
•Disease stabilization rate defined as the percentage of patients whose cancer
does not grow or shrink during
study treatment
•Safety of study treatment defined by the number and seriousness of adverse
events associated with brivanib
•Evaluation of biomarkers (such as Collagen IV, soluble VEGF and VEGF*receptor,
or soluble FGF) isolated
from patient blood samples and correlated with the clinical course of disease
and response to study
treatment
Background summary
Brivanib is a small molecule tyrosine kinase potent inhibitor of the vascular
endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family of
receptors. Its clinical development is focused in three main areas; VEGF driven
tumors, VEGF resistant tumors with targeting of FGF signaling pathways, and FGF
driven tumor biology. This trial is the proof of principle trial to demonstrate
that brivanib has activity when given as a single agent to subjects with
advanced solid tumors where the tumor over-expresses FGF-2 ligand protein as
demonstrated by immunohistochemistry.
Study objective
Compare Progression Free Survival (PFS) for brivanib versus placebo in subjects
with advanced solid tumors with FGF-2 over-expression and who have obtained
stable disease after 12 weeks of treatment with brivanib separately for each
tumor.
Study design
The main purpose of the study is to determine the effects of brivanib versus
placebo in patients with stable disease after 12 weeks of brivanib treatment.
Those patients who during the 12 weeks have clearly showed benefit will
continue treatment with brivanib and those who*s tumour has progressed will
come off study. For those patients in which it is unclear if they are
benefiting ie stable disease, half will continue on treatment and half will
stop treatment and switch to placebo. If the patient becomes substantially
worse on placebo they can restart brivanib treatment.
The study is divided into two parts. The initial phase is an open label lead-in
which has been designed to determine which patients to include or exclude from
the second randomised portion of the study which focuses on investigating which
patients are likely to benefit from treatment.
All tumour types will be considered with initial focus on advanced non-small
cell lung, transitional cell carcinoma, soft tissue sarcoma,
gastric/oesophageal adenocarcinoma or pancreatic cancer including ampulla of
Vater tumours. Should any tumour type have a low proportion of subjects
randomised into the second phase then the Study Steering Committee may cease
enrolment for that tumour type and another tumour type may be substituted,
these include: refractory prostate cancer, ovarian cancer, breast cancer,
endometrial cancer, melanoma, or head and neck cancer.
All qualifying patients will receive a daily dose of brivanib for up to 12
weeks. At the week 12 visit, if the tumour is assessed as stable according to
the Modified WHO criteria the patient will enter the double blind part of the
trial where they will be assigned to receive either brivanib or placebo at a
1:1 ratio stratified according to tumour type and FGF-2 status. For those
patients who show a >=50% reduction in tumour size they will continue on
brivanib treatment open-label. For those who show a >= 25% increase in tumour
size they will stop treatment and discontinue from the study.
Intervention
All subjects will receive brivanib during the initial 12 week run in period.
Subjects achieving stable disease at week 12 will be randomized to either
brivanib or matching placebo. Brivanib (BMS-582664) or placebo will be
self-administered orally on a continuous daily schedule of 800 mg until disease
progression or unacceptable toxicity.
Study burden and risks
There is a possibility that BMS-582664 may be an effective treatment for some
types of cancer. However, it is not known if individual patients entering the
trial will benefit directly. The information gained from this study may help
future patients with advanced cancer. Patients will have the inconvenience of
more frequent interventions/procedures and longer visits to the hospital than
would be usual for routine clinical care. They will also have to undergo
additional procedures. Potential side effects are known from research studies
in a small number of subjects. Additional unforeseen side effects could occur
and some side effects could be life-threatening or fatal. Safety monitoring is
included throughout the protocol. At all times throughout the study, the
patient has the right to withdraw consent without their usual standard of care
being affected.
Vijzelmolenlaan 9
3447 GX Woerden
NL
Vijzelmolenlaan 9
3447 GX Woerden
NL
Listed location countries
Age
Inclusion criteria
• Histologic or cytologic confirmed diagnosis of a solid tumor (non-small cell lung, gastric/esophageal adenocarcinoma, soft tissue sarcoma, transitional cell carcinoma and pancreatic cancer including ampulla of Vater tumors) which has progressed on standard therapy or for whom no standard therapy is known.
• Measurable disease
• Men and women, age 18 or older
• Life expectancy at least 3 months
• ECOG performance status 0 or 1 (generally fit and mobile)
• Adequate tumor sample for FGF-2 assay
• Adequate bone marrow, renal and hepatic function
• Adequate recovery from recent surgery and radiation therapy - one week for minor surgery and 8 weeks for major surgery or radiation therapy.
• At least 3 weeks must have relapsed since last dose of chemotherapy or targeted agents providing the subject has recovered from all toxicities. At least 8 weeks must have elapsed from the last dose of bevacizumab, prior to beginning protocol therapy.
Exclusion criteria
• Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy during study and up to 12 weeks after the last dose of drug, are pregnant or breastfeeding or have a positive pregnancy test on enrollment or prior to investigational product administration.
• Sexually active fertile men not using effective birth control if their partners are WOCBP, including up to 12 weeks after the last dose of investigational product.
• Actual diagnosis of brain metastasis or any known signs and symptoms, unless confirmed negative by means of a CT scan.
• Centrally cavitating lung lesions.
• History of thrombo-embolic disease within the last six months requiring therapy.
• Other primary malignancy except carcinoma in situ of cervix or urinary bladder or non-melanoma skin cancer.
• History of poor wound healing or non healing ulcers
• Uncontrolled or significant cardiovascular disease including myocardial infarction within 12 months, uncontrolled angina within 12 months; congestive heart failure (Class III-IV New York Heart Association (NYHA) and valvular heart disease grade 2.
• Uncontrolled hypertension even despite appropriate treatment.
• History of stroke, transient ischemic attack or other ischemic event.
• Mental incapacitation or psychiatric illness which would preclude study participation.
• Inability to swallow tablets or untreated malabsorption syndrome.
• History of allergy to brivanib its drug class or related compounds.
• Exposure to any investigational drug within 4 weeks of enrollment
• Other concurrent chemotherapy, hormonal therapy, immunotherapy regimens or radiotherapy, standard or investigational. Subjects may continue to receive hormone replacement therapy.
• Prior exposure to brivanib.
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 | EUCTR2008-000087-16-NL |
| ClinicalTrials.gov | NCT00633789 |
| CCMO | NL22044.078.08 |