Study of Lutetium-177 Labeled cG250 in Patients With Advanced Renal Cancer

This study has been completed.
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00142415
First received: August 31, 2005
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to determine whether 177Lutetium-DOTA-cG250 is effective for treatment of patients with advanced renal cell carcinoma


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: 111-In-DOTA-cG250
Drug: 177-Lu-DOTA-cG250
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Increasing Doses of Lutetium-177 Labeled Chimeric Monoclonal Antibody cG250 in Patients With Advanced Renal Cancer

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • To determine the safety of increasing doses of 177Lu-DOTA-cG250 in patients with advanced renal cancer to establish the MTD [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • To determine the targeting and dosimetry of 177Lu-DOTA-cG250 in patients with advanced renal cancer, using 111In-DOTA-cG250 as a surrogate. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response using RECIST criteria [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: February 2005
Study Completion Date: July 2013
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1, 30 mCi/m2 177-Lu-DOTA-cG250
Patients in the first arm received 10 mg of cG250 coupled to DOTA and labeled with 30 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 2, 40 mCi/m2 177-Lu-DOTA-cG250
Patients in the second arm received 10 mg of cG250 coupled to DOTA and labeled with 40 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 3, 50 mCi/m2 177-Lu-DOTA-cG250
Patients in the third arm received 10 mg of cG250 coupled to DOTA and labeled with 50 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 4, 60 mCi/m2 177-Lu-DOTA-cG250
Patients in the fourth arm received 10 mg of cG250 coupled to DOTA and labeled with 60 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 5, 70 mCi/m2 177-Lu-DOTA-cG250
Patients in the fifth arm received 10 mg of cG250 coupled to DOTA and labeled with 70 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177
Experimental: Cohort 6, 65 mCi/m2 177-Lu-DOTA-cG250
Patients in the sixth arm received 10 mg of cG250 coupled to DOTA and labeled with 65 mCi/m2 of 177-Lu-DOTA-cG250, once.
Drug: 111-In-DOTA-cG250
At day 1, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with 5 mCi of 111-Indium (111-In).
Other Names:
  • cG250
  • DOTA-cG250
  • cG250-In111
Drug: 177-Lu-DOTA-cG250
At day 8, every patient received the cG250 at a dose of 10 mg coupled to DOTA and labeled with a dose of 177-Lutetium (177-Lu) that started at 10 mCi by square meter for the patients of the 1st cohort.
Other Names:
  • cG250
  • DOTA-cG250
  • cG200-Lu177

Detailed Description:

This is a Phase I/II dose escalation study using 177Lu-DOTA-cG250 for treatment of patients with advanced renal cell carcinoma. The trial requires a minimum of 6 patients and a maximum of 18 patients. The initial group of patients will be treated with 30 mCi/m2 of Lu-177. Subsequent treatments will be in 10 mCi/m2 increments. At least three patients per dose level will be followed for up to 12 weeks with imaging, biochemical and hematologic tests to determine the safety of 177Lu-DOTA-cG250. CT scans will be carried out at baseline and after 12 weeks (or after recovery from toxicity), for response assessment.

Patients will initially receive 5 mCi/10 mg 111Indium-DOTA-cG250 antibody (an imaging dose preceeding Lu-177-cG250 treatment). Whole body and blood measurements of radioactivity will be obtained on at least three occasions for one week to determine targeting and dosimetry. Only if at least one known and evaluable metastatic lesion is visualized with In-111-cG250, therapeutic 177Lu-DOTA-cG250 will be administered the following week. In the absence of disease progression and after recovery from toxicity, patients may be retreated no sooner than 12 weeks after the prior treatment with a dose of no more than 75% of the previous dose, for a total of not more than three treatments. Only patients who have normal pharmacokinetics on the preceding diagnostic In-111-cG250 study (indicative of HACA negativity) are eligible for retreatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with proven advanced and progressive renal cell carcinoma of the clear cell type
  2. At least one evaluable lesion less than 5 cm
  3. Performance status: Karnofsky > or equal 70 %
  4. Laboratory values obtained less than 14 days prior to registration:

    • White blood cells (WBC) > or equal 3.5 x 109/l
    • Platelet count > or equal 100 x 109/l
    • Hemoglobin > or equal 6 mmol/l
    • Total bilirubin < or equal 2 x upper limit of normal (ULN)
    • ASAT, ALAT < or equal 3 x ULN (< 5 x ULN if liver metastases present)
    • Serum creatinine < or equal 2 x ULN
  5. Negative pregnancy test for women of childbearing potential (urine or serum)
  6. Age over 18 years
  7. Ability to provide written informed consent

Exclusion Criteria:

  1. Known metastases to the brain
  2. Untreated hypercalcemia
  3. Metastatic disease limited to the bone
  4. Pre-exposure to murine/chimeric antibody therapy
  5. Chemotherapy, external beam radiation or immunotherapy within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed, when unirradiated, evaluable lesions elsewhere are present.
  6. Cardiac disease with New York Heart Association classification of III or IV
  7. Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception
  8. Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgement of the investigator will significantly affect patients' clinical status
  9. Life expectancy shorter than 6 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00142415

Locations
Netherlands
University Medical Center Nijmegen
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Radboud University
Investigators
Principal Investigator: W.J.G. Oyen, MD, PhD Department of Nuclear Medicine, University Medical Center Nijmegen
Principal Investigator: P.F.A. Mulders, MD, PhD Department of Urology, University Medical Center Nijmegen
  More Information

No publications provided by Ludwig Institute for Cancer Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00142415     History of Changes
Other Study ID Numbers: LUD2003-006
Study First Received: August 31, 2005
Last Updated: December 30, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Ludwig Institute for Cancer Research:
Advanced Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma (CCRCC)
Lutetium-177
177-Lu
cG250
DOTA-cG250
Monoclonal Antibody

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014