Trial Information

Blood Test for Ovarian Cancer Associated Auto Antibodies

Since the mutations of a normal cell that lead to a malignancy, involves changes in the
structure and function of the cells, it could be assumed that the immune system has
recognized some of these changes as antigenic determinates that should be responded against.
For many years, investigators tried to distinguish between cancer patients and healthy
population by the difference in specific autoantibodies level. In the healthy population, a
baseline of the amount of autoantibodies was determined, and the patient population had to
have a statistically significant higher level of autoantibodies. The presence of
autoantibodies in all population in different levels made it very difficult to find these
specifically discriminating antibodies. To date, no specific autoantibody is distinguishing
solely between healthy and cancer patients (as opposed to autoimmune diseases, where
specific autoantibodies can be found in very high levels in patients only).

Our work assumes that specific Autoantibodies expression level should be altered in cancer,
and thus these changes can indicate the presence / absence of cancer.

In this experiment protocol, we are checking for changes in expression levels of specific
autoantibodies of women with ovarian pathology compared to women without cancer.

The CAAA test is comprised of a blood collection and processing step followed by detection
of specific auto antibodies with an ELISA based assay and a mathematical processing, with a
subsequent classification of the results as "positive" or "negative" for ovarian cancer.

The study population includes those women that are scheduled for a pathological or
cytological confirmation either by a surgical procedure (laparoscopy/laparotomy) or any kind
of biopsy or cytology, prior to any anti-cancer treatment and aged matched controls. The
clinical suspicion includes one of the following: Pelvic mass/cyst (by pelvic examination
and/or imaging techniques), and/or high CA-125 levels, and/or ascites, and/or due to
incidental finding of distant metastasis. Final verification ("true positive" or "true
negative") will be done in relation to pathology/cytology results only or for healthy women
in relation to clinical history.

Subject Selection Suspected ovarian cancer women(patients and non-cancers women) - Inclusion
criteria - all of the following

- 18 years or over.

- Patients suspected of ovarian pathology. The clinical suspicion will include one of the
following: Pelvic mass/cyst (by pelvic examination and/or other imaging techniques),
and/or high CA-125 levels, and/or ascites, and/or due to incidental finding of distant
metastasis. Final analysis will be done in relation to pathology/cytology results only.

- Patients scheduled laparotomy/laparoscopy/surgery, ideally before any of the above.

Suspected ovarian cancer women(patients and non-cancers women) - Exclusion criteria: any of
the following

- Less than 18 years of age

- Hematological malignancies

- Autoimmune disorders diagnosed patients.

- Previous or current tumors

- Patients under active chemotherapy treatment

Suspected ovarian cancer patients - final classification

• The "true positive" group consists of all sequential patients that satisfy inclusion
criteria and are positive for ovarian cancer by pathology results. The "true negative" group
consists of sequential patients that satisfy inclusion criteria and are negative for ovarian
cancer by pathology results.

This study will be based on multi-centers participation. The minimum number of sites for the
study is 2.

The current study is a single blind prospective validation study, involving all consecutive
suspected ovarian pathology women being scheduled for biopsy/surgery during the study
duration, having pathology/cytology ovarian cancer (true positive) and XXX number of women
having negative ovarian pathology/cytology results (true negative)and healthy women. The
purpose of the study is to evaluate the effectiveness of the CAAA test.

The effectiveness of the study is defined as the specificity of the CAAA test for a pre
defined sensitivity of 95%.

The study will evaluate the sensitivity of CAAA test to show that it is not below the
declared level of 95%.

According to current medical publications, we assume that the study population will include
about 10-20% of true positive cancer cases.

As of today, large proportion of the suspected patients was only diagnosed by final
pathology of the laparoscopy/surgery. In this study, the true positive and true negative
cases (as verified by pathology) will be compared to the CAAA test results.

Study Procedure Subjects clinical information acquired from the patient's medical file,
including age, medical history and results of tests done leading to the diagnostic
evaluation of ovarian cancer will be recorded on the appropriate, bar-coded, pre-study case
report forms .The reports will be electronic via a dedicated and secured internet site, any
changes in the database will be recorded and will be traceable. The study is anonymous and
the Department will keep the name of the patient without reveling it to investigators and to
the study sponsor.

The doctor/ nurse/ phlebotomist will collect a heparin vacuum/serological tube (about 8ml),
label (bar-code) them. The blood handling laboratory will collect serum/plasma and the
serum will be kept frozen at -80C.

ELISA based tests for the detection of Auto Antibodies relative expression ratios, will be
conducted on each sample according to the lab protocol . The samples will be tested for
response to the antigens that have been identified on a previous training set. All the data
will be permanently recorded directly into a dedicated computer. For each sample all
antibody results will be put into the coded patient file. A mathematical algorithm will
determine if the sample is positive or negative.

The final pathology will be compared with the CAAA test results. The results will be
analyzed by a statistician with expertise in cancer population studies.

The current study is a blind prospective validation study, involving all consecutive
suspected ovarian pathology subjects being scheduled for biopsy/surgery/cytology during the
study duration. The purpose of the study is to assess the sensitivity and specificity of the
CAAA test for detection ovarian cancer in women scheduled for biopsy/surgery/cytology.

Subjects will be screened for potential participation in the study, according to the
inclusion and exclusion criteria.

The data will include parameters of the clinical and pathological/cytological state of the
subjects and results of CAAA ELISA.

There are two goals of the study. To test that the sensitivity of CAAA is not below the
pre-defined level. To evaluate the specificity of CAAA test. Statistical Hypothesis The main
condition determining the sample size is to validate that the sensitivity of the test is not
lower than the predefined level. The classification rule was established in such a way that
the sensitivity in the teaching sample was 100%. We assume that the real sensitivity is not
lower that 99%.

Null Hypothesis: The sensitivity of the test is not higher than 95%. A database management
system shall be designed and maintained, including screen preparation, and edit check
programming. Pre-entry and post-entry quality control of the clinical data shall be
performed at each data entry center. All ELISA test results will be uploaded to the database
via an internet based interface, and will be locked against further changes. In order to
change ELISA test results, unlocking of the database requires consent from the local CRO,
the sponsor and the site physician. Unlocking will be done only by the webmaster, and will
be recorder in the tracing system component, and in a hard copy held both by the sponsor and
the CRO in the site.