Although Neopharm has terminated its sponsorship of this study, it is continuing under the
sponsorship of the NCI. Please contact Raffit Hassan, MD at 301-451-8742 for more
information. Also see the related NCI study "Experimental Drug SS1(dsFv)-PE38 to Treat
Cancer" (Study ID number 010011).
SS1(dsFv)-PE38 is an oncology drug product containing a bacteria toxin, fused to a high
affinity, disulfide stabilized antibody. The fused protein retains cell killing activity,
but binds only to cells expressing mesothelin. Tumors characterized by very high surface
mesothelin expression include mesothelioma; epithelial carcinomas of ovary and peritoneum;
and squamous cancers of cervix and upper aerodigestive tract, including esophagus, head, and
This is a dose-escalating study to determine the maximum tolerated dose (MTD) of intravenous
SS1(dsFv)-PE38 administered once every other day for six doses. Dose escalation will
proceed in cohorts of 3 until dose-limiting toxicity (DLT) is observed.
OBJECTIVES: I. Determine the toxicities and maximum tolerated dose (MTD) of six doses of
SS1(dsFv)-PE38 QOD administered by intravenous infusion to patients with advanced
II. Characterize the plasma pharmacokinetics of SS1(dsFv)-PE38 after intravenous infusion.
III. Determine toxicities attributable to subsequent courses of SS1(dsFv)-PE38.
IV. Evaluate the response of selected advanced malignancies to intravenous infusion of six
doses of SS1(dsFv)-PE38 QOD administered at the MTD.
V. Determine the induction of antibody against SS1(dsFv)-PE38 and its relationship to
PROTOCOL OUTLINE: To exclude immediate allergic hypersensitivity reaction, each patient will
receive a test dose of SS1(dsFv)-PE38, and be observed for 30 minutes prior to receiving
study dosing. Each treatment will be given by intravenous infusion over 30 minutes every
other day. Hydration will be maintained. (Oral hydration may be adequate, but intravenous
hydration may be used at the Investigator?s discretion.) Patients will be observed for at
least 4 hours after infusion on Day 1 of each treatment course to exclude immediate allergic
reaction. Treatment may be repeated for a maximum of two additional courses after 4 weeks
if re-treatment criteria are met. At least three patients will be accrued at each dose
level. Dose escalation within a patient will not be allowed.
PROJECTED ACCRUAL: Up to 30 patients
Histopathologic diagnosis of one of the following malignancies: ovarian carcinoma, all
non-mucinous epithelial histologies, including primary peritoneal and fallopian tube
carcinoma; malignant mesothelioma, except sarcomatous histology; squamous cell cancer of
the lung; squamous cell cancer of the cervix; or squamous cell cancer of the head and
Tissue block must be available for analysis. Tumor, initial or recurrent, must be
positive (at least 30% of tumor cells) for mesothelin by immunohistochemistry.
Recurrent unresectable disease after appropriate definitive therapy.
At least 4 weeks elapsed since any prior therapy, with recovery from side effects. No
concurrent anti-tumor treatment of any kind.
Measurable or evaluable tumor documented within 4 weeks prior to study entry.
At least 18 years of age.
At least 12-week life expectancy.
Performance Status (ECOG) 0-2.
Adequate organ function, including: Absolute neutrophil count at least 1,500/mm3;
Platelets at least 75,000/mm3; Creatinine, Calcium, and total Bilirubin less than or equal
to the upper limit of normal; Liver enzymes AST and ALT less than or equal 2.5 x the upper
limit of normal; Albumin at least 3.0 g/dL; Oxygen (O2) saturation more than 93% (room
Informed Consent signed in accordance with institutional criteria.
No known central nervous system (CNS) or spinal cord involvement by tumor.
No detectable antibody to SS1(dsFv)-PE38.
No concurrent antitumor therapy.
No cardiovascular condition NY Heart Association Grade II-IV, or any
clinically-significant pericardial effusion.
No infection requiring parenteral antibiotics; no HIV infection; and no seropositivity for
Hepatitis B and Hepatitis C.
Must not be pregnant or nursing. Females of child-bearing potential must use an effective
method of contraception.