Protocol Number: 01-C-0011

Title:

Phase I Study of SS1 (dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion For 10 Days

Number:

01-C-0011

Summary:

This study will determine the dose of the experimental anticancer drug SS1(dsFv)-PE38 that can be given safely to patients. It will also look at how the body handles the drug, its side effects, and its effect on the tumor. SS1(dsFv)-PE38 will be tried in patients with solid tumors that have an antigen called mesothelin. This is a protein that is normally produced by cells lining body cavities, but has also been found on several types of cancer cells. The drug SS1(dsFv)-PE38 is composed of SS1, a protein that binds tightly to mesothelin, and PE38, parts of the Pseudomonas exotoxin (PE) protein, which can kill human cells if it gains entry to them. SS1(dsFv)-PE38 is designed to attach to mesothelin on the cancer cells and allow entry of the PE38, which will then destroy the cells.

Patients 18 years of age and older with malignant mesothelioma or cancer of the head, neck, lung, cervix or ovaries may be eligible for this study. Candidates will have a medical history, physical examination, blood and urine tests, electrocardiogram (EKG) and chest X-ray, and tumor evaluation with computerized tomography (CT) scans or other imaging tests.

Participants will receive SS1(dsFv)-PE38 intravenously (through a vein) for 10 consecutive days. Weight and vital signs (temperature, heart and breathing rate and blood pressure) will be recorded and blood tests will be done during and after the treatment to look for side effects. Physical exams and blood and urine tests will be done to evaluate side effects weekly for two weeks, or more often if side effects occur. Depending on side effects, treatments may be repeated every 4 weeks for a maximum of four treatments. Physical examinations and blood and urine tests will be repeated with each treatment, and X-rays or CT scans will be done four weeks after each treatment to measure the effect of treatment on the tumor. An EKG will be repeated after three courses of treatment, or sooner if treatment is stopped. After the final treatment, follow-up visits will be scheduled at 3-month intervals.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Histopathologic diagnosis of one of the following malignancies:

Malignant mesothelioma;

Ovarian carcinoma, all epithelial histologies, including primary peritoneal and fallopian tube carcinoma. This includes tumors involving ovary and also bowel, which could possibly have originated from bowel, such as appendiceal carcinoma.

Pancreatic cancer;

Squamous cell cancer of the lung;

Squamous cell cancer of the head and neck;

Squamous cell cancer of the cervix.

Recurrent unresectable disease in patients who have received or are unwilling to receive standard therapies or anticancer therapies that are expected to prolong survival and improved quality of life.

Tumor (initial or recurrent; greater than or equal to 30% of tumor cells) must be positive (at least 1+) for mesothelin by immunohistochemistry.

No concurrent anti-tumor treatment. At least 4 weeks since any prior anti-tumor therapy, with recovery from side effects and at least one week since any hematopoetic growth factor therapy.

Measurable or evaluable tumor documented within 4 weeks prior to study entry.

Age greater than or equal to 18 years.

Life expectancy greater than or equal to 12 weeks.

Performance Status (ECOG) 0-2.

Adequate organ function, including:

ANC greater than or equal to 1,000/mm(3); Plts greater than or equal to 75,000/mm(3);

Creatinine less than or equal to Institutional Upper Limit Normal (ULN) or Creatinine less than or equal to 2.0 mg/dL if 24-hour urinary Creatinine Clearance is greater than or equal to 50 cc/min, Ca (2+) and total Bilirubin less than or equal to upper limit normal (ULN); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN;

Albumin greater than or equal to 3.0 gm/dL;

S0(2) greater than 92% (room air).

Sign informed consent, in accordance with institutional criteria.

EXCLUSION CRITERIA:

Patient may not have any of the following:

Any known CNS or spinal cord involvement by tumor.

Detectable antibody to SS1 (dsFv)-PE38.

Concurrent antitumor therapy.

Cardiovascular condition NY Heart Association Grade II-IV, or any clinically-significant pericardial effusion.

An infection requiring parenteral antibiotics, HIV infection, or seropositivity for Hepatitis B and Hepatitis C.

Be pregnant or nursing. Females of child-bearing potential must use an effective method of contraception.

Special Instructions: Currently Not Provided

Keywords:

Recombinant Protein

Monoclonal Antibody

Fusion Toxin

Targeted Immunotherapy

Mesothelioma

Recruitment Keywords:

None

Conditions:

Mesothelioma

Ovarian Neoplasm

Squamous Cell Neoplasm

Investigational Drug(s):

SS1 (dsFv)-PE38

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

Improving antibody affinity by mimicking somatic hypermutation in vitro

Characterization of the antigen (cak1) recognized by monoclonal antibody k1 present on ovarian cancers and normal mesothelium

Isolation and characterization of a monoclonal antibody

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