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

Study Overview
=================
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.

Official Title
-----------------
A Phase I Study of Yttrium-90 Labeled Humanized Anti-CEA M5A Antibody in Patients With CEA Producing Advanced Malignancies

Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Other: high performance liquid chromatography
* Other: pharmacological study
* Procedure: radionuclide imaging
* Procedure: single photon emission computed tomography
* Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-90-DOTA-M5A anti-CEA antibody<br> | Other: high performance liquid chromatography<br>* Performed on serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples<br>Other: pharmacological study<br>* Serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples<br>Procedure: radionuclide imaging<br>* 1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post Y-90 anti-CEA antibody infusion<br>Procedure: single photon emission computed tomography<br>* 2 days and 3-5 days post antibody infusion<br>Radiation: yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A<br>* Dose escalation from 12 mCi/m2 through 18 mCi/m2 increasing by 2 mCi/m2 with each escalation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | 10 weeks after the beginning of the last cycle of treatment | 
| Toxicity |  | From the date of the beginning of the first cycle of treatment to 10 weeks from the date of the beginning of the last cycle of treatment | 
| Overall survival |  | From 3 months after treatment completion or until death | 
| Progression-free survival |  | From 3 months after treatment completion until cancer progression or start of another treatment | 
| Time to progression |  | 3 months and six months after treatment completion until cancer progression or start of another treatment | 
| Pharmacokinetic and molecular studies |  | At 0, 1, 4-6, 12-24, 48, 72-120 and 144-168 hours after administration of the baseline imaging dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified adult solid tumor, protocol specific