RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver
tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating
patients who have relapsed or refractory small cell lung cancer.
- Determine the dose limiting toxicity and maximum tolerated dose of yttrium Y 90
anti-CEA monoclonal antibody MN-14 in patients with relapsed or refractory small cell
- Determine the dosimetric and pharmacokinetic properties of this treatment regimen in
the blood, normal organs, and tumors of these patients.
- Determine the stability and complexation with circulating carcinoembryonic antigen of
this radioantibody in the plasma of these patients.
- Determine the antibody response of these patients treated with this regimen.
- Determine the antitumor effects of this treatment regimen in these patients.
OUTLINE: This is a dose escalation study of yttrium Y 90 anti-CEA monoclonal antibody MN-14
(90Y-hMN-14). Patients are stratified according to prior radiotherapy (yes vs no).
Patients undergo pretherapy imaging with indium In 111 anti-CEA monoclonal antibody MN-14 IV
over 30-40 minutes on day -7 or -6 followed by external scintigraphy on days -7 or -6 to 0.
Patients who show positive localization of at least one documented tumor site receive
90Y-hMN-14 IV over 30-40 minutes on day 0.
Cohorts of 3-6 patients receive escalating doses of 90Y-hMN-14 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose limiting toxicity.
Patients are followed at 2, 4, 8, and 12 weeks; every 3 months for 2 years; and then every 6
months for 3 years.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 10-14
- Histologically or cytologically confirmed small cell lung cancer (SCLC)
- Must have received at least one prior course of standard chemotherapy and, if
indicated, up to 6,900 cGy of thoracic radiotherapy
- Patients who received prior radiotherapy must show evidence of progressive
- Patients who received no prior radiotherapy to the primary tumor must show
evidence of stable or progressive disease
- Measurable disease
- Must have evidence of carcinoembryonic antigen (CEA) production or expression
documented by one of the following:
- Serum CEA at least 10 ng/mL
- Positive immunohistology of either the primary tumor or a metastasis with CEA
specific monoclonal antibody
- Must have unilateral bone marrow biopsy with less than 25% tumor involvement
- No known, active brain metastases
- 18 and over
- Karnofsky 70-100%
- ECOG 0-2
- At least 3 months
- WBC at least 3,000/mm^3
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2 mg/dL
- AST no greater than 2 times upper limit of normal (ULN)
- No hepatitis B or C
- No other serious liver abnormality
- Creatinine no greater than 1.5 times ULN
- No urinary incontinence
- Ejection fraction at least 50%
- FEV_1 and FVC at least 60%
- DLCO at least 50% predicted
- No severe anorexia, nausea, or vomiting
- No other significant medical problems
- No prisoners
- No reactivity to humanized MN-14 (in patients with prior exposure to chimeric or
- HIV negative
- No active HIV-related disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3 months
following study participation
PRIOR CONCURRENT THERAPY:
- See Chemotherapy
- No concurrent growth factors (e.g., filgrastim [G-CSF])
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy
- No prior high dose chemotherapy with stem cell transplantation
- Not specified
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy
- Prior radiotherapy to less than 30% of red marrow (including standard chest x-ray for
limited stage SCLC) allowed
- At least 4 weeks since prior major surgery