Clinical trial NCT00006981: Immunotoxin Therapy in Treating Patients With Advanced Cancer
Official title: Phase I Study Of SS1(dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion X 10 Days
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: recurrent non-small cell lung cancer
stage III cervical cancer
recurrent cervical cancer
stage IVB cervical cancer
stage IVA cervical cancer
squamous cell lung cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
advanced malignant mesothelioma
recurrent malignant mesothelioma
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent metastatic squamous neck cancer with occult primary
ovarian undifferentiated adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian serous cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian clear cell cystadenocarcinoma
cervical squamous cell carcinoma
metastatic squamous neck cancer with occult primary squamous cell carcinoma
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
fallopian tube cancer
primary peritoneal cavity cancer
ovarian carcinosarcoma
Brenner tumor
untreated metastatic squamous neck cancer with occult primary
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
ovarian mucinous cystadenocarcinoma
borderline ovarian surface epithelial-stromal tumor
ovarian sarcoma
ovarian stromal cancer
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
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 an effective treatment for advanced cancer.

PURPOSE: Phase I trial to study the effectiveness of immunotoxins in treating patients who have advanced cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose and toxic effects of SS1(dsFv)-PE38 immunotoxin in patients with advanced malignancies that express mesothelin.

Secondary

* Determine the response in patients treated with this drug.
* Determine the plasma pharmacokinetics of this drug in these patients.

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

Patients receive SS1(dsFv)-PE38 immunotoxin IV continuously on days 1-10. Treatment repeats every 4 weeks for a maximum of 4 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 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignancy, including one of the following:

  * Malignant mesothelioma
  * Ovarian epithelial carcinoma (mucinous or nonmucinous), including primary peritoneal or fallopian tube carcinoma

    * Tumors that may have originated in the bowel (e.g., appendiceal carcinoma) and involve the ovary
    * Ovarian cancers of other histology are eligible provided they express mesothelin
  * Pancreatic cancer
  * Squamous cell lung cancer
  * Squamous cell cancer of the head and neck
  * Squamous cell cancer of the cervix
* Recurrent unresectable disease after prior standard anticancer therapy that was expected to prolong survival and improve quality of life OR unwilling to receive standard anticancer therapy
* At least 30% of initial or recurrent tumor cells positive (at least 1+) for mesothelin by immunohistochemistry
* Measurable or evaluable disease
* No known CNS or spinal cord involvement
* No clinically significant pericardial effusion

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,000/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

Renal:

* Creatinine no greater than ULN OR
* Creatinine no greater than 2.0 mg/dL if creatinine clearance at least 50 mL/min
* Calcium no greater than ULN

Cardiovascular:

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

Pulmonary:

* Oxygen saturation (SO_2) more than 92% on room air

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No detectable antibody to SS1(dsFv)-PE38
* No infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 1 week since prior hematopoietic growth factor therapy

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* At least 4 weeks since any prior antitumor 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
Study officials:
affiliation: National Cancer Institute (NCI)
name: Robert Kreitman, MD
role: STUDY_CHAIR
References:
citation: Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res. 2009 Aug 15;15(16):5274-9. doi: 10.1158/1078-0432.CCR-09-0062. Epub 2009 Aug 11.
citation: Hassan R, Kreitman R, Strauss L, et al.: SS1(dsFv)-PE38 anti-mesothelin immunotoxin in advanced malignancies: phase I and pharmacokinetic study of alternate-day infusion. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-113, 2002.
citation: Kreitman R, Squires D, O'Hagan D, et al.: SS1(dsFv)-PE38 anti-mesothelin immunotoxin in advanced malignancies: phase I study of continuous infusion. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1896, 2002.