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

Lung Cancer Clinical Trial

Official title:

Phase I Non-Myeloablative Trial With 90Y-Humanized MN-14 (Anti-CEA) Antibody for Relapsed or Refractory Small Cell Lung Cancer (SCLC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00006347
• Other study ID #: CDR0000068199
• Secondary ID: CMMI-C-057A-99NC
• Status: Active, not recruiting
• Phase: Phase 1
• First received: October 4, 2000
• Last updated: February 28, 2009
• Start date: August 2000

Study information

• Verified date: April 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Radiation:
• indium In 111 monoclonal antibody MN-14

• yttrium Y 90 monoclonal antibody MN-14

Locations

Country	Name	City	State
United States	Garden State Cancer Center	Belleville	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Garden State Cancer Center at the Center for Molecular Medicine and Immunology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,