AzTrials
AzTrials

Metastatic Renal Cell CarcinomaPhase 1/2NCT00142415

Phase I/II Dose-escalation Study of Lutetium-177-labeled cG250 in Patients With Advanced Renal Cancer

A Phase 1/2 study testing 111-In-DOTA-cG250 and 177-Lu-DOTA-cG250 in people with Metastatic Renal Cell Carcinoma, run by Ludwig Institute for Cancer Research at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was a Phase I/II, single-center, dose-escalation study. 177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250 (177-Lu-DOTA-cG250) was administered at a starting dose of 30 mCi/m^2 of 177-Lu (fixed dose of 10 mg cG250) and escalated in increments of 10 mCi/m^2 of 177-Lu in sequentially… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
111-In-DOTA-cG250 and 177-Lu-DOTA-cG250
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteNetherlands
Study dates
Feb 2005to Jan 2011
Phase
Phase 1/2
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with proven advanced and progressive renal cell carcinoma (RCC) of the clear cell type.
  • At least one evaluable lesion < 5 cm.
  • Karnofsky performance status ≥ 70%.
  • Laboratory values obtained < 14 days prior to registration:
  • White blood cells (WBC) ≥ 3.5 × 10^9/L
  • Platelet count ≥ 100 × 10^9/L
Show all 13Show fewer
  • Hemoglobin ≥ 6 mmol/L
  • Total bilirubin ≤ 2 × upper limit of normal (ULN)
  • Aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN (< 5 × ULN if liver metastases present)
  • Serum creatinine ≤ 2 × ULN
  • Negative pregnancy test for women of childbearing potential (urine or serum).
  • Age over 18 years.
  • Ability to provide written informed consent.

Who cannot join

  • Known metastases to the brain.
  • Untreated hypercalcemia.
  • Metastatic disease limited to the bone.
  • Pre-exposure to murine/chimeric antibody therapy.
  • Chemotherapy, external beam radiation or immunotherapy within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures was allowed, when unirradiated, evaluable lesions were present elsewhere.
  • Cardiac disease with New York Heart Association classification of III or IV.
Show all 9Show fewer
  • Subjects who were pregnant, nursing or of reproductive potential and were not practicing an effective method of contraception.
  • Any unrelated illness, e.g., active infection, inflammation, medical condition or laboratory abnormality, that in the judgement of the investigator would have significantly affected the subject's clinical status.
  • Life expectancy < 6 months.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Nijmegen

    Nijmegen, 6500HB

Other trials in Netherlands

About this study

Official title: Phase I/II Study of Increasing Doses of Lutetium-177 Labeled Chimeric Monoclonal Antibody cG250 (177^Lu-DOTA-cG250) in Patients With Advanced Renal Cancer

This was a Phase I/II, single-center, dose-escalation study. 177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250 (177-Lu-DOTA-cG250) was administered at a starting dose of 30 mCi/m^2 of 177-Lu (fixed dose of 10 mg cG250) and escalated in increments of 10 mCi/m^2 of 177-Lu in sequentially enrolled cohorts according to a standard 3 + 3 design until determination of the maximum tolerated dose (MTD). The primary objectives were to determine the safety, targeting, and dosimetry of 177-Lu-DOTA-cG250 in subjects with advanced renal cell carcinoma. The secondary objective was measurement of tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Read the detailed description

Prior to administration of 177-Lu-DOTA-cG250, subjects received 5 mCi/10 mg of the 111-Indium-DOTA-cG250 (111-In-DOTA-cG250) antibody (an imaging dose). Whole body and blood measurements of radioactivity were obtained on at least 3 occasions for 1 week to determine targeting and dosimetry. If at least one known and evaluable metastatic lesion was visualized with 111-In-DOTA-cG250, a single dose of therapeutic 177-Lu-DOTA-cG250 was administered the following week. In the absence of disease progression and after recovery from toxicity, subjects may have been retreated no sooner than 12 weeks after the previous treatment with a dose of no more than 75% of the previous dose, for a total of not more than 3 treatments. Only subjects with normal pharmacokinetics on the diagnostic 111-In-DOTA-cG250 study (indicative of human anti-chimeric antibody [HACA] negativity) were eligible for re-treatment.

Subjects in the initial cohort were enrolled sequentially to receive 30 mCi/m^2 of 177-Lu-DOTA-cG250 (fixed dose of 10 mg cG250). In the absence of a dose-limiting toxicity, the dose was escalated in each subsequent cohort in 10 mCi/m^2 increments of 177-Lu. At least 3 subjects per dose level were followed for up to 12 weeks with imaging, biochemical, and hematologic tests. Safety was monitored continuously throughout the study.

Being tested
111-In-DOTA-cG250, 177-Lu-DOTA-cG250
Keywords
Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma (CCRCC), Lutetium-177, 177-Lu, cG250, DOTA-cG250, Monoclonal Antibody
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 111-In-DOTA-cG250Drug

    Also called cG250, DOTA-cG250, cG250-In111

    On Day 1, each subject received a single intravenous (IV) infusion of 10 mg of cG250 coupled to DOTA and labeled with 5 mCi of 111-In.

  • 177-Lu-DOTA-cG250Drug

    Also called cG250, DOTA-cG250, cG200-Lu177

    On Day 8, 9, or 10, each subject received a single IV infusion of 10 mg of cG250 coupled to DOTA and labeled with a dose of 177-Lu at a starting dose of 30 mCi/m^2 in the initial cohort.

Study groups in NCT00142415
Study groupRoleWhat they receive
Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250
Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250
Cohort 3, 50 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250
Cohort 4, 60 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250
Cohort 5, 70 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250
Cohort 6, 65 mCi/m^2 177-Lu-DOTA-cG250ExperimentalSubjects received an initial single dose of 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m^2 of 177-Lu.
Receives: Drug: 111-In-DOTA-cG250; Drug: 177-Lu-DOTA-cG250

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Treatment-emergent Adverse Events

    Toxicity was graded in accordance with the NCI CTCAE version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.

    Measured: Up to 1 year

  2. Number of Subjects With Dose-limiting Toxicity (DLT) During Cycle 1

    Subjects were monitored for AEs for ≥ 8 weeks after the last infusion of 177-Lu-DOTA-cG250 before dose escalation could be implemented. Toxicity was graded in accordance with the NCI CTCAE version 3.0. DLT was defined as the following treatment-related events: ≥ Grade 3 non-hematologic toxicity; ≥ Grade 4 hematologic toxicity (platelets < 25 × 10^9/L or leukocytes < 1.0 × 10^9/L) that persisted for > 4 weeks except anemia; thrombocytopenia < 10 × 10^9/L; clinically relevant myelotoxicity that required hospitalization and/or blood product transfusion (e.g., uncontrolled bleeding, infections that had to be treated clinically).

    Measured: 12 weeks

  3. Radiation Absorbed Doses by Organ for 177-Lu-cG250

    After each 177-Lu-cG250 administration, 3 whole-body scintigrams were acquired (directly after injection and 2-4 days and 5-7 days post-injection) and blood samples were drawn at 5, 30, 60, and 120 min, 2-4 days, and 5-7 days post-infusion. Estimated radiation absorbed doses were calculated according to the Medical Internal Radiation Dose scheme, which permits estimation of the factors required to calculate dose to one organ attributable to a source in another organ.

    Measured: 12 weeks

Secondary outcomes (1)

  1. Number of Subjects With Best Overall Tumor Response

    Tumor responses were evaluated using computed tomography and categorized according to RECIST v1.0 at baseline and at the end of every cycle (every 12 weeks) or after recovery from toxicity. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

    Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2005 (estimated)
  2. Study startFeb 2005
  3. Primary completionJan 2011
  4. Study completionJan 2011

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00142415
Sponsor's protocol ID
LUD2003-006
Status last verified
Oct 2022
First submitted
31 Aug 2005
Last updated
28 Oct 2022
Data monitoring committee
No
Individual data sharing
Yes: Data have been published

Publications

  • Stillebroer AB, Boerman OC, Desar IM, Boers-Sonderen MJ, van Herpen CM, Langenhuijsen JF, Smith-Jones PM, Oosterwijk E, Oyen WJ, Mulders PF. Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma. Eur Urol. 2013 Sep;64(3):478-85. doi: 10.1016/j.eururo.2012.08.024. Epub 2012 Aug 21.

    PubMed 22980441

  • Stillebroer AB, Zegers CM, Boerman OC, Oosterwijk E, Mulders PF, O'Donoghue JA, Visser EP, Oyen WJ. Dosimetric analysis of 177Lu-cG250 radioimmunotherapy in renal cell carcinoma patients: correlation with myelotoxicity and pretherapeutic absorbed dose predictions based on 111In-cG250 imaging. J Nucl Med. 2012 Jan;53(1):82-9. doi: 10.2967/jnumed.111.094896. Epub 2011 Dec 12.

    PubMed 22159179

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 111-In-DOTA-cG250 and 177-Lu-DOTA-cG250 in people with Metastatic Renal Cell Carcinoma, run by Ludwig Institute for Cancer Research at 1 site in Netherlands.

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 13 inclusion and 9 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 28 Oct 2022. 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 Netherlands. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 22 Mar 2017). 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 Subjects With Treatment-emergent Adverse Events (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00142415, which also lists 2 linked publications.

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 28 Oct 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in