Monoclonal Antibody Therapy in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer

NCT ID: NCT00006347

Last Updated: 2009-03-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-08-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

• 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 lung cancer.
• 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 months.

Conditions

Lung Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

indium In 111 monoclonal antibody MN-14

Intervention Type: RADIATION

yttrium Y 90 monoclonal antibody MN-14

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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 disease
• 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

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/mm^3
• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

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%

Pulmonary:

• FEV_1 and FVC at least 60%
• DLCO at least 50% predicted

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
• 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:

Biologic therapy:

• See Chemotherapy
• No concurrent growth factors (e.g., filgrastim [G-CSF])

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No prior high dose chemotherapy with stem cell transplantation

Endocrine therapy:

• Not specified

Radiotherapy:

• 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

Surgery:

• At least 4 weeks since prior major surgery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

OTHER

Sponsor Role: lead

Principal Investigators

Jack D. Burton, MD

Role: STUDY_CHAIR

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

Locations

Garden State Cancer Center

Belleville, New Jersey, United States

Countries

United States

Other Identifiers

CMMI-C-057A-99

Identifier Type: -

Identifier Source: secondary_id

NCI-H00-0064

Identifier Type: -

Identifier Source: secondary_id

CDR0000068199

Identifier Type: -

Identifier Source: org_study_id