VM110 in Detection of Microscopic Tumors: A Phase I Study

Current methods of imaging techniques, CT, MRI and PET, fail to detect moderate volume of
diffuse intraperitoneal tumor and provide limited functional information. White light
laproscopy is capable of detecting small volume disease in only half of patients in clinical
remission, missing occult disease in 30% of this patient population. In this study, a
synthetic agent VM110 is to be tested for its ability to detect occult ovarian and pancreatic
cancers. The agent is cleaved by proteases, cathepsin B, L, and S and plasmin in cancer cells
and the fluorescent cleavage product is detected by near infra red imaging probe. High
sensitivity of visualizaion of cancer cells can help detect sub-clinical disease otherwise
unidentifiable by usual methods.

Primary Objectives

1. To investigate the safety and toxicity of escalating doses of VM110 administered IV
prior to laparoscopic surgery.

2. To define the appropriate dose of VM110 for use in future trials.

3. To define the preliminary efficacy: the optimal dose of VM110 in detection of
microscopic peritoneal tumor at laparoscopy not visible with standard white light
laparoscopy. Areas visible with both standard white light and NIRF light, and areas
visible only with NIRF light will be biopsied. Data from pathologic evaluation of these
specimens will be used to determine the efficacy of VM110 with respect to its ability to
detect occult disease not visible with standard white light

Secondary Objectives

1. Estimate sensitivity and specificity of VM110 detection

2. Perform correlative pharmacologic and histopathological analyses

Inclusion Criteria:

1. Patients with known or suspected pancreatic or ovarian carcinoma who will be
undergoing clinically appropriate laparoscopic evaluation or treatment. Patients will
not undergo laparoscopy solely for the purpose of participation in this trial.

2. Patients must have evidence of disease either through elevation of tumor markers or
radiologic evidence of disease

3. Patient may be male or female and of any race / ethnicity.

4. Participation in this trial will not significantly alter pre-surgical, surgical or
post-surgical care

5. ECOG PS of 0-1

6. Patients should be free of active infection requiring antibiotics

7. Any therapy directed at the malignant tumor, including immunologic agents, must be
discontinued at least three weeks prior to registration

8. Patients must have adequate:

- Renal function: serum creatinine less than or equal to 1.5 x institutional upper
limit normal (ULN)

- Hepatic function: Total bilirubin less than or equal to 1.5 x ULN , SGOT and
alkaline phosphatase less than or equal to 2.5 x ULN

- PTT (partial thromboplastin time) ≤ 1x ULN and INR ≤ 1.5 x ULN.

9. Women of child-bearing potential (WOCBP), defined as all women physiologically capable
of becoming pregnant, must use highly effective methods of contraception during the
study and 8 weeks after. Highly effective contraception methods include combination of
any two of the following:

1. Use of oral, injected or implanted hormonal methods of contraception, or;

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;

4. Total abstinence or;

5. Male/female sterilization

10. Women are considered post-menopausal and not of child-bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior
to randomization. In the case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow up hormone level assessment is she
considered not of child-bearing potential.

a. Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
contraception, during the study and for 8 weeks after the end of treatment

11. Age ≥ 18

12. Capable of complying with study procedures and communicating with study personnel.

13. Patients must have signed an approved informed consent and authorization permitting
release of personal health information. Ability to understand and willingness to sign
a written informed consent and HIPAA consent document

Exclusion Criteria:

1. Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded. Prior radiation for localized cancer of the breast, head and
neck, or skin is permitted, provided that it was completed more than three years prior
to registration, and the patient remains free of recurrent or metastatic disease.

2. Patients with an active bleeding diathesis or on oral anti-vitamin K medication
(except low-dose warfarin used for catheter-related thrombosis prophylaxis).

3. Prior history of hypersensitivity to Pegylated liposomal doxorubicin or ICG allergy.
Caution should be taken if prior ICG allergy is noted.

4. Pregnant or nursing (lactating) women

5. History of congestive cardiac failure or an EKG suggesting significant conduction
defect, or myocardial ischemia, or active psychiatric disease requiring treatment that
would interfere with the understanding or conduct of the study.

6. Subject has previously received VM110, or any other investigational product in the
past thirty days.

7. Inadequate tumor sites or volume to allow for biopsy per standard of care.

8. Patients with psychiatric or other conditions rendering them incapable of
participating in informed consent or the requirements of this protocol or other
condition or personal circumstance that, in the judgment of the investigator, might
interfere with the collection of complete good quality data.