Yttrium Y 90 DOTA Anti-CEA Monoclonal Antibody M5A in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00645060

Last Updated: 2020-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-09
• Study Completion Date: 2016-09-06

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for advanced cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A in treating patients with advanced solid tumors.

Detailed Description

OBJECTIVES:

• To establish the maximum tolerated dose of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A and describe the toxicities at each dose studied.
• To estimate radiation doses to whole body, normal organs, and tumor through serial nuclear imaging studies after intravenous infusion of the yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A.

OUTLINE: This is a dose-escalation study of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A (MOAB M5A).

• Biodistribution: Patients receive indium In 111 radiolabeled anti-CEA MOAB M5A IV over 30 minutes. Patients undergo serial nuclear scans, single photon emission computed tomography (SPECT), and blood and urine sampling over 1 week to estimate absorbed radiation doses to tumor, normal organs (i.e., liver, lung, kidney, and bone marrow), and whole body.
• Treatment: No more than 2 weeks later, patients with adequate biodistribution receive yttrium Y 90 DOTA anti-CEA MOAB M5A IV over 30 minutes on day 1. Patients then undergo serial nuclear scans, SPECT, and blood and urine sampling over 1 week to estimate absorbed radiation doses to tumor, normal organs (i.e., liver, lung, kidney, and bone marrow), and whole body. Treatment repeats every 6-10 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected periodically for analysis of total activity by radiometric high performance liquid chromatography and to acquire data on antibody metabolism and pharmacokinetics.

After completion of study treatment, patients are followed every 3 months for up to 6 months.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Y-90-DOTA-M5A anti-CEA antibody

Group Type: EXPERIMENTAL

high performance liquid chromatography

Intervention Type: OTHER

Performed on serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples

pharmacological study

Intervention Type: OTHER

Serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples

radionuclide imaging

Intervention Type: PROCEDURE

1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post Y-90 anti-CEA antibody infusion

single photon emission computed tomography

Intervention Type: PROCEDURE

2 days and 3-5 days post antibody infusion

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A

Intervention Type: RADIATION

Dose escalation from 12 mCi/m2 through 18 mCi/m2 increasing by 2 mCi/m2 with each escalation

Interventions

high performance liquid chromatography

Performed on serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples

Intervention Type: OTHER

pharmacological study

Serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples

Intervention Type: OTHER

radionuclide imaging

1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post Y-90 anti-CEA antibody infusion

Intervention Type: PROCEDURE

single photon emission computed tomography

2 days and 3-5 days post antibody infusion

Intervention Type: PROCEDURE

yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A

Dose escalation from 12 mCi/m2 through 18 mCi/m2 increasing by 2 mCi/m2 with each escalation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Tumors must produce CEA as documented by either an elevated serum CEA above the upper limit of normal (ULN) or by immunohistochemical (IHC) methods

• Positive CEA IHC stain is determined if more than 30% of the tumor cells have an intensity of 2+ or greater
• Measurable disease
• Estimated < 1/3 of liver involvement if tumor involves the liver
• No brain or leptomeningeal involvement with cancer

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 3 months
• WBC ≥ 4,000/μL
• ANC ≥ 1,500/μL
• Platelet count ≥ 125,000/μL
• Creatinine ≤ 1.5 mg/dL and/or creatinine clearance > 60 mL/min
• Bilirubin ≤ 1.5 mg/dL
• ALT and AST ≤ 2 times ULN
• Negative pregnancy test
• Fertile patients must use effective contraception
• Patients currently being treated for severe infections or recovering from other intercurrent illnesses (such as poorly controlled diabetes or hypertension) are ineligible until recovery is deemed complete by the investigator
• Serum anti-antibody testing must be negative for human anti-humanized antibodies (if patient received prior monoclonal antibody)
• Serum HIV-negative
• Serum hepatitis B antigen- and hepatitis C antibody-negative

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior radiotherapy, immunotherapy, or chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
• Recovered from prior major surgery
• No prior radiotherapy to > 50% of bone marrow
• No other concurrent chemotherapy, radiotherapy, or immunotherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Y. Wong, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Stephen I. Shibata, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-05198

Identifier Type: -

Identifier Source: secondary_id

CDR0000590300

Identifier Type: REGISTRY

Identifier Source: secondary_id

05198

Identifier Type: -

Identifier Source: org_study_id