The primary objective of this study is to determine the overall survival (OS) of single agent OSI-906 (Arm A) versus placebo (Arm B) in patients with adrenocortical carcinoma (ACC) who received at least 1 but no more than 2 prior drug regimens.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the overal survival of OSI-906 (arm A) versus placebo (arm b) in
patients with adrenocortical carcinoma who received at least 1 but no more than
2 prior drug regimens.
Secondary outcome
• progression-free survival, disease control rate, best overall response rate,
and duration of response;
• quality of life
• the safety profile of OSI-906;
• the pharmacokinetic profile of OSI-906; and
• pharmacodynamic changes and correlations with treatment outcome.
Background summary
ACC is a very aggressive tumor without effective therapy options. Median
survival in metastasized disease is less than 15 months. Thus far, mitotane is
the only therapy approved for treatment of ACC and there is currently no
standard of care for second- or third-line treatment of locally
advanced/metastatic disease. OSI-906 is a small molecule that is a potent
inhibitor of IGF-1R tyrosine kinase activity. The overexpression of IGF-2 that
is frequently observed in ACC could lead to activation of both IGF-1R and the
insulin receptor A (IR-A) isoform. OSI-906 has inhibitory activity against both
IGF-1R and IR-A. OSI-906 might therefore be expected to have more activity in
ACC.
Study objective
The primary objective of this study is to determine the overall survival (OS)
of single agent OSI-906 (Arm A) versus placebo (Arm B) in patients with
adrenocortical carcinoma (ACC) who received at least 1 but no more than 2 prior
drug regimens.
Study design
Approximately 135 adult patients worldwide will be randomized in 45 centers.
This is a multicenter, randomized, double-blind, placebo-controlled, phase 3
study. The study exist of a screening visit and a treatment period. If the
patient is eligible, the patient has to visit the clinic once every 3 weeks as
long as the patients receives OSI-906/placebo. Every visit takes approximately
4 hours. The patient will be asked on day 1 and day 22 to stay at the clinic
for a time period of 8 hours. During the first 3 weeks the patient has to visit
the clinic or another location once a week for blood examination. The treatment
period is 21 days. When the patient is still in study after 6 months, the
treatment period will become 42 days.
Intervention
Blood draws, urine collection and if needed a biopsy.
Study burden and risks
OSI-906 can, besides the possible effect on cancer cells, also have an effect
on several organs or others parts of the body.
Based on early results from human studies, the following events are now
considered to be related to OSI-906:
• Elevated blood sugar (glucose)
• Nausea
• Vomiting
• Tiredness or fatigue
• Rash
• Itchiness
• Diarrhoea
In non-human studies, an effect of OSI-906 included:
• May effect the electrical activity of the heart which rarely may lead to a
serious abnormality of your heart rhythm.
As with any drug, an allergic reaction is possible; some allergic reactions can
be life-threatening. There may also be side effects that we don*t know about
yet.
Other potential risks include:
The most common side effects associated with taking blood samples from the arm
through a vein may include discomfort or pain where the needle is introduced,
redness, bruising, light-headedness, bleeding at the puncture site and on rare
occasions infections.
Fasting (not eating or drinking for several hours) before blood draws can cause
dizziness, headaches, stomach discomfort or fainting.
Dexamethasone (a steroid) may be given as a single dose for the dexamethasone
suppression test. A single moderate dose of oral dexamethasone is not expected
to have any significant side effects except possibly some nausea. Severe
allergic reactions are rare. However, long term use of dexamethasone is
associated with many significant side effects. You should discuss any concerns
with your study doctor.
PREGNANCY / CONTRACEPTION
The effect that OSI-906 may have on an unborn or nursing baby is not known.
Pregnant women must not take part in this study; neither should women who plan
to become pregnant or who are breast-feeding a baby. Women who can have
children will be asked to have a pregnancy test before taking part to exclude
the possibility of pregnancy. Both women and men (and their partners), who are
sexually active and possibly fertile, will be asked to use an effective means
of birth control while taking part in this study.
3 Parkway North
60015, Deerfield, IL
US
3 Parkway North
60015, Deerfield, IL
US
Listed location countries
Age
Inclusion criteria
- Histologically confirmed adrenocortical carcinoma that is locally advanced or metastatic and not amenable to surgical resection.
- Measurable disease according to RECIST (version 1.1).
- Radiologically-confirmed progressive disease within 6 months prior to randomization.
- Age >= 18 years .
- Predicted life expectancy >= 12 weeks.
- At least 1 but no more than 2 prior drug regimens (including molecular targeted therapy, systemic cytotoxic chemotherapy, biologics, and/or vaccines) for locally advanced/metastatic ACC. A minimum of 3 weeks must have elapsed between the end of prior treatment and randomization. All patients must have received prior mitotane, either as neoadjuvant, adjuvant, or locally advanced/metastatic therapy. Adjuvant and neoadjuvant mitotane therapy will not be counted as prior drug regimens or as systemic cytotoxic chemotherapy.
Exclusion criteria
- Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy.
- Prior IGF-1R inhibitor therapy.
- History of prior malignancy, except for resected basal cell or squamous cell carcinoma of the skin, cured in situ cervical carcinoma, cured ductal carcinoma in situ of the breast, or other cancers where the patient has been disease-free for >= 3 years.
- History of significant cardiovascular disease unless the disease is well-controlled.
- History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability.
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 | EUCTR2009-012820-97-NL |
| ClinicalTrials.gov | NCT00924989 |
| CCMO | NL29658.015.09 |