Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer
Study Details
Study Description
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 |
|---|---|---|
|
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
- 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.
Study Design
Arms and Interventions
| 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 Names:
Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Names:
|
| 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 Names:
Biological: 111In-hu3S193
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Dose-limiting Toxicities (DLTs) [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
- Clearance as Measured by the Half-life (T1/2) of the Elimination Phase [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.
- Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment [Up to day 56]
Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Histologically confirmed non-mucinous ovarian adenocarcinoma.
-
Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer.
-
Patients with residual disease < 2cm will be candidates for this study.
-
The following laboratory and clinical results within the last 2 weeks prior to study day 1:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet count ≥ 100 x 109/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%;
-
Karnofsky performance status ≥ 70.
-
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.
-
Placement of an intra-abdominal catheter at the time of surgery.
Exclusion Criteria
-
Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification).
-
Presence of symptomatic extra abdominal metastases.
-
Known central nervous system (CNS) tumor involvement.
-
Clinically significant heart disease (New York Heart Association Class III or IV).
-
ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction.
-
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.
-
Chronic inflammatory bowel disease.
-
Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment.
-
Pregnancy or lactation.
-
Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
- Principal Investigator: Chaitanya R. Divgi, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000339682
- MSKCC-03069
- LUD2001-018
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. |
| Period Title: Overall Study | ||
| STARTED | 3 | 4 |
| COMPLETED | 3 | 1 |
| NOT COMPLETED | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Total of all reporting groups |
| Overall Participants | 3 | 4 | 7 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
66.7%
|
2
50%
|
4
57.1%
|
| >=65 years |
1
33.3%
|
2
50%
|
3
42.9%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
100%
|
4
100%
|
7
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
1
25%
|
1
14.3%
|
| Not Hispanic or Latino |
3
100%
|
3
75%
|
6
85.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
25%
|
1
14.3%
|
| White |
3
100%
|
3
75%
|
6
85.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
3
100%
|
4
100%
|
7
100%
|
Outcome Measures
| Title | Number of Patients With Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | 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. |
| Time Frame | Up to day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who entered the study. |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. |
| Measure Participants | 3 | 4 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Clearance as Measured by the Half-life (T1/2) of the Elimination Phase |
|---|---|
| Description | 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. |
| Time Frame | Up to 22 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who entered the study and had serum samples taken at the specified times. Patient No. 5 in Cohort 2 did not have Day 22 blood drawn and was not included in the mean value. |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. |
| Measure Participants | 3 | 3 |
| Mean (Full Range) [days] |
2.43
|
2.28
|
| Title | Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment |
|---|---|
| Description | Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE. |
| Time Frame | Up to day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients who entered the study. |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. |
| Measure Participants | 3 | 4 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | up to 56 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All adverse events occurring during the study were recorded on the patient's case report form. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). | |||
| Arm/Group Title | Cohort 1 | Cohort 2 | ||
| Arm/Group Description | Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5 mCi 111In-hu3S193 to enable imaging after dosing. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | 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. 90Y-hu3S193: Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. 111In-hu3S193: Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | ||
All Cause Mortality |
||||
| Cohort 1 | Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/4 (0%) | ||
Serious Adverse Events |
||||
| Cohort 1 | Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/4 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cohort 1 | Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 3/4 (75%) | ||
| Cardiac disorders | ||||
| Dizziness | 1/3 (33.3%) | 0/4 (0%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal disorder | 1/3 (33.3%) | 0/4 (0%) | ||
| Nausea | 2/3 (66.7%) | 1/4 (25%) | ||
| Constipation | 1/3 (33.3%) | 0/4 (0%) | ||
| Abdominal pain | 0/3 (0%) | 1/4 (25%) | ||
| General disorders | ||||
| Fatigue | 1/3 (33.3%) | 0/4 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic function abnormal | 1/3 (33.3%) | 0/4 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatremia | 0/3 (0%) | 1/4 (25%) | ||
| Renal and urinary disorders | ||||
| Incontinence | 0/3 (0%) | 1/4 (25%) | ||
| Reproductive system and breast disorders | ||||
| Pelvic pain | 1/3 (33.3%) | 0/4 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mary Macri, Senior Director, Clinical Trials Management |
|---|---|
| Organization | Ludwig Institute for Cancer Research |
| Phone | 12124501546 |
| mmacri@lcr.org |
- CDR0000339682
- MSKCC-03069
- LUD2001-018