Ovarian CancerPhase 1NCT00072410
Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer
A Phase 1 study testing 90Y-hu3S193 and 111In-hu3S193 in people with Ovarian Cancer, run by Ludwig Institute for Cancer Research at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- 90Y-hu3S193 and 111In-hu3S193
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to 15 Nov 2006
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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%;
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
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
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.
Read the 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.
- Conditions
- Ovarian Cancer
- Being tested
- 90Y-hu3S193, 111In-hu3S193
- Keywords
- recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
90Y-hu3S193Biological
Also called humanized monoclonal antibody 3S193 radiolabeled with 90Y
Patients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y.
111In-hu3S193Biological
Also called humanized monoclonal antibody 3S193 radiolabeled with 111In
Patients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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. Receives: Biological: 90Y-hu3S193; Biological: 111In-hu3S193 |
| Cohort 2 | Experimental | 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. Receives: Biological: 90Y-hu3S193; Biological: 111In-hu3S193 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose-limiting Toxicities (DLTs)
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.
Measured: Up to day 56
Secondary outcomes (2)
Clearance as Measured by the Half-life (T1/2) of the Elimination Phase
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.
Measured: Up to 22 days
Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment
Blood samples were taken at baseline and on days15, 28 and 56. HAHA was measured by BIACORE.
Measured: Up to day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2003 (estimated)
- Study startNov 2003
- Primary completionMay 2005
- Study completion15 Nov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Chaitanya R. Divgi, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00072410
- Sponsor's protocol ID
- CDR0000339682
- Other IDs
- MSKCC-03069, LUD2001-018
- Status last verified
- Oct 2023
- First submitted
- 4 Nov 2003
- Last updated
- 4 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00072410
- Acronym / sponsor ID
- CDR0000339682
- Conditions
- Ovarian Cancer
- Keywords
- recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2003 (actual)
- Primary completion
- May 2005 (actual)
- Study completion
- 15 Nov 2006 (actual)
- First posted
- 6 Nov 2003 (estimated)
- Results
- Posted 21 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: 90Y-hu3S193, Biological: 111In-hu3S193Patients 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. |
| Cohort 2 | Experimental | Biological: 90Y-hu3S193, Biological: 111In-hu3S193Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 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%;
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 90Y-hu3S193Also: humanized monoclonal antibody 3S193 radiolabeled with 90YPatients received a single dose of 10 mg of hu3S193 radiolabeled with the intended dose (mCi) of 90Y. | Biological | Cohort 1, Cohort 2 |
| 111In-hu3S193Also: humanized monoclonal antibody 3S193 radiolabeled with 111InPatients received a single dose of 5 mCi 111In-hu3S193 together with the 90Y-hu3S193. | Biological | Cohort 1, Cohort 2 |
Primary outcome
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.
2 secondary outcomes
Clearance as Measured by the Half-life (T1/2) of the Elimination Phase
Time frame: Up to 22 days
Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment
Time frame: Up to day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chaitanya R. Divgi, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 90Y-hu3S193 and 111In-hu3S193 in people with Ovarian Cancer, run by Ludwig Institute for Cancer Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Dose-limiting Toxicities (DLTs) (time frame: Up to day 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.