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

City of Hope

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Other: high performance liquid chromatography

Procedure: radionuclide imaging

Other: pharmacological study

Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A

Procedure: single photon emission computed tomography

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00645060

P30CA033572 (U.S. NIH Grant/Contract)

CDR0000590300 (Registry Identifier)

CHNMC-05198

05198

Details and patient eligibility

About

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.

Full 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.

Enrollment

18 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed advanced solid tumor for which no standard or effective treatment is available
- Patients who refuse an available standard but non-curative treatment may also be eligible
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