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Trial record 6 of 7 for:    hu3s193

Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00072410
Recruitment Status : Completed
First Posted : November 6, 2003
Results First Posted : December 21, 2021
Last Update Posted : December 21, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Brief Summary:

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. Giving radiolabeled monoclonal antibody directly into the abdominal cavity may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of giving radiolabeled monoclonal antibody therapy directly into the abdominal cavity in treating patients who have advanced ovarian epithelial cancer.


Condition or disease Intervention/treatment Phase
Ovarian Cancer Biological: 90Y-hu3S193 Biological: 111In-hu3S193 Phase 1

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and maximum tolerated dose of intraperitoneally (IP) administered yttrium-90 (90Y) radiolabeled monoclonal antibody (mAB) hu3S193 (90Y-hu3S193) in patients with advanced ovarian epithelial cancer.

Secondary

  • Determine the localization and whole body and abdominal clearance of 90Y-hu3S193 using indium-111 (111In) radiolabeled hu3S193 and gamma camera imaging.
  • Determine the serum pharmacokinetics of hu3S193 using gamma well counting.
  • Determine the antibody response as measured by human anti-human antibody response (HAHA).

OUTLINE: This is a dose-escalation study of the yttrium-90 radiolabeled monoclonal antibody, 90Y-hu3S193.

Patients received technetium (99mTc-sulfur colloid) IP and underwent abdominal imaging on day 1. Provided the distribution of the 99mTC-sulfur colloid was deemed adequate, patients then received 90Y-hu3S193 IP. 111In-hu3S193 was also administered IP over 30 minutes on day 1 to enable gamma camera imaging. Within 3-5 hours after antibody administration, patients underwent whole body imaging and single-photon emission-computed tomography (SPECT) imaging of the abdomen and pelvis.

Cohorts of 3-6 patients were to receive escalating doses of 90Y-hu3S193 until the maximum tolerated dose (MTD) was determined. The MTD was defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients were to be followed every 3 months for at least 2 years and then every 6 months for up to 5 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-Dose, Cohort Study of Increasing Doses of Yttrium-90 Conjugated to Humanized Monoclonal Antibody 3S193 (90Y-hu3S193) in Patients With Advanced Ovarian Cancer
Actual Study Start Date : November 2003
Actual Primary Completion Date : May 2005
Actual Study Completion Date : November 15, 2006


Arm Intervention/treatment
Experimental: Cohort 1
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
Biological: 90Y-hu3S193
Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.
Other Name: humanized monoclonal antibody 3S193 radiolabeled with 90Y

Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Name: humanized monoclonal antibody 3S193 radiolabeled with 111In

Experimental: Cohort 2
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
Biological: 90Y-hu3S193
Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.
Other Name: humanized monoclonal antibody 3S193 radiolabeled with 90Y

Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Name: humanized monoclonal antibody 3S193 radiolabeled with 111In




Primary Outcome Measures :
  1. Number of Patients With Dose-limiting Toxicities (DLTs) [ Time Frame: Up to day 56 ]

    All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT was defined as:

    • Any Grade 3 or greater non-hematological toxicity (except for alopecia, nausea, and vomiting, defined separately below)
    • Any Grade alopecia
    • Grade 4 nausea or vomiting ≥ 5 days duration.
    • Any Grade 4 hematological toxicity (except for toxicity of ≤ 5 days duration without growth factor, platelet, or transfusion support). To be dose limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.


Secondary Outcome Measures :
  1. Clearance as Measured by the Half-life (T1/2) of the Elimination Phase [ Time Frame: Up to 22 days ]
    Serum samples were taken 5 min, 1 hour, and 2 hours after end of infusion, twice on study day 2, and daily on study days 3 to 7, 8, 15 and 22. Serum samples were analyzed in a gamma well counter. Elimination half-life (T1/2) was generated by fitting effective clearance to a monoexponential curve.

  2. Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment [ Time Frame: Up to day 56 ]
    Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Histologically confirmed non-mucinous ovarian adenocarcinoma.
  2. Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer.
  3. Patients with residual disease < 2cm will be candidates for this study.
  4. The following laboratory and clinical results within the last 2 weeks prior to study day 1:

    Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L; Serum bilirubin ≤ 2.0 mg/dL; Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum creatinine ≤2.0 mg/dL; Forced expiratory volume (FEV1) ≥60% of predicted; Forced vital capacity (FVC) ≥60% of predicted; Diffusion capacity ≥55% of predicted; Left ventricular ejection fraction (LVEF) ≥50%;

  5. Karnofsky performance status ≥ 70.
  6. Before any trial-specific procedures or treatment can be performed, the patient or legally authorized guardian or representative must give witnessed written informed consent for participation in the trial.
  7. Placement of an intra-abdominal catheter at the time of surgery.

Exclusion Criteria

  1. Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification).
  2. Presence of symptomatic extra abdominal metastases.
  3. Known central nervous system (CNS) tumor involvement.
  4. Clinically significant heart disease (New York Heart Association Class III or IV).
  5. ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction.
  6. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders that may limit the amount of antibody they can tolerate or render them ineligible for surgery.
  7. Chronic inflammatory bowel disease.
  8. Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment.
  9. Pregnancy or lactation.
  10. Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00072410


Locations
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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Ludwig Institute for Cancer Research
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Chaitanya R. Divgi, MD Memorial Sloan Kettering Cancer Center
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Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00072410    
Other Study ID Numbers: CDR0000339682
MSKCC-03069 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
LUD2001-018 ( Other Identifier: Ludwig Institute for Cancer Research )
First Posted: November 6, 2003    Key Record Dates
Results First Posted: December 21, 2021
Last Update Posted: December 21, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ludwig Institute for Cancer Research:
recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents