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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00645060
First received: March 26, 2008
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Yttrium-90 Labeled Humanized Anti-CEA M5A Antibody in Patients With CEA Producing Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 10 weeks after the beginning of the last cycle of treatment ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: From 3 months after treatment completion or until death ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From 3 months after treatment completion until cancer progression or start of another treatment ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 3 months and six months after treatment completion until cancer progression or start of another treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetic and molecular studies [ Time Frame: At 0, 1, 4-6, 12-24, 48, 72-120 and 144-168 hours after administration of the baseline imaging dose ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: October 2006
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00645060

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Jeffrey Y. Wong, MD Beckman Research Institute
Principal Investigator: Stephen I. Shibata, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00645060     History of Changes
Other Study ID Numbers: 05198, P30CA033572, CHNMC-05198, CDR0000590300
Study First Received: March 26, 2008
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014