Clinical trial NCT00072410: Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-11-06
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Patients With Dose-limiting Toxicities (DLTs)
timeFrame: Up to day 56
Secondary outcomes:
measure: Clearance as Measured by the Half-life (T1/2) of the Elimination Phase
timeFrame: Up to 22 days
measure: Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment
timeFrame: Up to day 56
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Chaitanya R. Divgi, MD
role: PRINCIPAL_INVESTIGATOR
References: