Clinical trial NCT00066651: Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors
Official title: Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Fallopian Tube Cancer
Head and Neck Cancer
Lung Cancer
Malignant Mesothelioma
Ovarian Cancer
Pancreatic Cancer
Primary Peritoneal Cavity Cancer
Keywords: ovarian carcinosarcoma
ovarian clear cell cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian serous cystadenocarcinoma
ovarian undifferentiated adenocarcinoma
recurrent ovarian epithelial cancer
Brenner tumor
primary peritoneal cavity cancer
fallopian tube cancer
epithelial mesothelioma
recurrent malignant mesothelioma
recurrent pancreatic cancer
cervical squamous cell carcinoma
recurrent cervical cancer
recurrent non-small cell lung cancer
squamous cell lung cancer
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent metastatic squamous neck cancer with occult primary
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the nasopharynx
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-08-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating advanced solid tumors.

PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy in treating patients with recurrent unresectable advanced solid tumors.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose of SS1(dsFv)-PE38 immunotoxin in patients with advanced mesothelin-expressing malignancies.

Secondary

* Determine the toxic effects of this drug in these patients.
* Determine the plasma pharmacokinetics of this drug in these patients.
* Determine the response in patients treated with this drug.
* Correlate the induction of antibody against this drug with its pharmacokinetics in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive a test dose of SS1(dsFv)-PE38 immunotoxin IV over 1-2 minutes on day 1 followed by SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SS1(dsFv)-PE38 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-15 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed advanced malignancy of 1 of the following types:

  * Ovarian cancer

    * All nonmucinous epithelial histologies are eligible
  * Primary peritoneal cavity cancer
  * Fallopian tube cancer
  * Malignant mesothelioma

    * No sarcomatous histology
  * Pancreatic cancer
  * Squamous cell cancer (SCC) of the lung
  * SCC of the cervix
  * SCC of the head and neck
* Recurrent unresectable disease, meeting 1 of the following criteria:

  * Previously treated with definitive standard therapy
  * Patient refused prior standard therapy
* Initial or recurrent tumor positive (at least 30% of tumor cells) for mesothelin by immunohistochemistry\* NOTE: \*Immunohistochemical evaluation not required for patients with pancreatic cancer
* Measurable or evaluable disease
* No clinically significant pericardial effusion
* No known CNS or spinal cord involvement by tumor

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 75,000/mm\^3

Hepatic

* Bilirubin no greater than upper limit of normal (ULN)
* AST and ALT no greater than 2.5 times ULN
* Albumin at least 3.0 g/dL
* Hepatitis B and C negative

  * Seropositive allowed if clinically asymptomatic
* except if clinically asymptomatic and bilirubin and AST and ALT meet the outlined criteria

Renal

* Creatinine no greater than ULN
* Calcium no greater than ULN

Cardiovascular

* No New York Heart Association class II-IV cardiovascular disease

Pulmonary

* Oxygen saturation at least 93% on room air
* DLCO at least 50% of predicted\*
* Total lung capacity and vital capacity at least 50% of predicted\*
* FEV_1 at least 50% of predicted\* NOTE: \*For patients with pleural mesothelioma and as clinically indicated

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No infection requiring parenteral antibiotics
* No HIV infection
* Serum neutralizing activity to SS1(dsFv)-PE38 immunotoxin (at 200 ng/mL) no greater than 75%

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* At least 4 weeks since prior therapy and recovered
* No other concurrent antitumor therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
Study officials:
affiliation: National Cancer Institute (NCI)
name: Raffit Hassan, MD
role: STUDY_CHAIR
References: