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 radiolabeled monoclonal antibody therapy in treating patients who have relapsed or refractory non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
Adenosquamous Cell Lung Cancer Squamous Cell Lung Cancer recurrent non-small cell lung cancer Adenocarcinoma of the Lung large cell lung cancer	Drug: indium In 111 monoclonal antibody MN-14  Drug: yttrium Y 90 monoclonal antibody MN-14	Phase I

Further Study Details: 

OBJECTIVES: I. 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 non-small cell lung cancer. II. Determine the dosimetric and pharmacokinetic properties of this treatment regimen in the blood, normal organs, and tumors of these patients. III. Determine the stability and complexation with circulating carcinoembryonic antigen of this radioantibody in the plasma of these patients. IV. Determine the antibody response of these patients with this treatment regimen. V. Determine the antitumor effects of this treatment regimen in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of yttrium Y 90 anti-CEA monoclonal antibody MN-14 (90Y-hMN-14). 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 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed non-small cell lung cancer; Adenocarcinoma, squamous large cell, or mixed cell histology; Patients with nonadenocarcinomatous 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 received at least one prior regimen of standard chemotherapy and, if indicated, no greater than 6,900 cGy thoracic radiotherapy
• Patients with stage IIIA/B unresectable disease who received prior radiotherapy must show evidence of progressive disease (greater than 25% increase in primary tumor or appearance of new lesions)
• Patients with stage IIIB or IV disease who received no prior radiotherapy to the primary or index lesion must show evidence of stable or progressive disease by CT scans at least 4 weeks apart
• Less than 25% tumor involvement in bone marrow
• No known, active brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: No prior stem cell transplantation after high-dose chemotherapy; No concurrent growth factors
• Chemotherapy: See Disease Characteristics; See Biologic; At least 4 weeks since prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; At least 4 weeks since prior radiotherapy; Prior radiotherapy to less than 30% of red marrow allowed
• Surgery: At least 4 weeks since prior major surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100% ECOG 0-2
• Life expectancy: At least 3 months
• Hematopoietic: WBC at least 3,000/mm3; Granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: 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
• Renal: Creatinine no greater than 1.5 times ULN; No urinary incontinence
• Cardiovascular: Ejection fraction at least 50% by MUGA
• Pulmonary: FEV1 at least 60% DLCO at least 50%
• Other: 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 humanized antibody); HIV negative; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for at least 3 months after study

New Jersey
      Garden State Cancer Center, Belleville,  New Jersey,  07103,  United States

Study chairs or principal investigators

Jack D. Burton,  Study Chair,  Garden State Cancer Center   

Study ID Numbers:  CDR0000068198; CMMI-C-047A-99; NCI-H00-0063
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 6, 2000
ClinicalTrials.gov Identifier:  NCT00006458
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08