Patient case: 49-year-old female with lung cancer; genetic feature: ERBB2

Clinical trial: Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

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: 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

Relevance to patient case: not relevant