Clinical trial NCT00645060: Yttrium Y 90 DOTA Anti-CEA Monoclonal Antibody M5A in Treating Patients With Advanced Solid Tumors
Official title: A Phase I Study of Yttrium-90 Labeled Humanized Anti-CEA M5A Antibody in Patients With CEA Producing Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 10 weeks after the beginning of the last cycle of treatment
measure: Toxicity
timeFrame: 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
measure: Overall survival
timeFrame: From 3 months after treatment completion or until death
measure: Progression-free survival
timeFrame: From 3 months after treatment completion until cancer progression or start of another treatment
measure: Time to progression
timeFrame: 3 months and six months after treatment completion until cancer progression or start of another treatment
measure: Pharmacokinetic and molecular studies
timeFrame: At 0, 1, 4-6, 12-24, 48, 72-120 and 144-168 hours after administration of the baseline imaging dose
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Jeffrey Y. Wong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: City of Hope Comprehensive Cancer Center
name: Stephen I. Shibata, MD
role: PRINCIPAL_INVESTIGATOR
References: