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

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

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.

Study Overview

• Status: Completed
• 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

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Y-90-DOTA-M5A anti-CEA antibody

Other: high performance liquid chromatography; Performed on serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples; Other: pharmacological study; Serial blood samples from 0 to 168 hours and daily X5 days 24 hour urine samples; Procedure: radionuclide imaging; 1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post Y-90 anti-CEA antibody infusion; Procedure: single photon emission computed tomography; 2 days and 3-5 days post antibody infusion; Radiation: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Y. Wong, MD, City of Hope Comprehensive Cancer Center; Principal Investigator: Stephen I. Shibata, MD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: October 9, 2006
• Primary Completion (Actual): September 6, 2016
• Study Completion (Actual): September 6, 2016

Study Registration Dates

• First Submitted: March 26, 2008
• First Submitted That Met QC Criteria: March 26, 2008
• First Posted (Estimate): March 27, 2008

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: 05198; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-05198; CDR0000590300 (Registry Identifier: NCI PDQ)