RITCOLON: Pretargeted Radioimmunotherapy in Metastatic Colorectal Cancer
Study Details
Study Description
Brief Summary
Phase I/II, Open-labeled, Prospective, Multi-center study of a Pretargeted Radioimmunotherapy in metastatic colorectal cancer with ractionated injections of TF2 plus 90Y-IMP288 (RITCOLON).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This study investigates a pretargeted radioimmunotherapy (pRAIT) with the anti-carcinoembryonic antigen (CEA) TF2 bispecific monoclonal antibody (BsMAb) and the 90Y-IMP288 radio-labeled peptide.
TF2 will be given once a week for 3 successive weeks at 75 mg/m2 per dose. IMP288 will be given 3 times, 1 day after each TF2 injection. IMP288 will be radio-labeled with 111In (imaging) for the first injection and then 90Y (therapy) for the 2 subsequent injections.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: several cohorts All patients will receive 3 injections of TF2 (the first: 14 mg/m², the second and the third:75 mg/m²). One day after each injection of TF2, the patient will receive a radiolabelled peptide (IMP-288) with Yttrium for therapeutic injectionThe First cohort will receive 555 MBq/m2 X 2 of 90-Y-IMP-288.: All patient will receive 180 MBq of 111-In-IMP-288 for dosimetry analysis |
Drug: Antibody TF2
injection of a recombinant antibody CEA specific. Three injections. Each injection are separate by one week
Drug: 90-Y-IMP-288
Injection of the peptide 90-Y-IMP-288, 24 Hours after injection of TF2. 2 injections by patients separated by one week (week 2 and week 3)
Drug: 111-In-IMP-288
Injection of the peptide 111-In-IMP-288, 24 Hours after the first injection of TF2 (week 1)
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Outcome Measures
Primary Outcome Measures
- To determine the maximum tolerated dose for 90Y-IMP288. [Week 6 to week 12]
toxicity analysis
Eligibility Criteria
Criteria
Inclusion Criteria:
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Metastatic colorectal cancer and failure to standard therapies (5-fluorouracil, irinotecan, oxaliplatin, anti-vascular endothelium growth factor, anti-epidermal growth factors in patients with RAS wild type tumors). A previous line with regorafenib is not required.
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Elevated CEA serum level or proved CEA expression in tumor tissue
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≥ 18 years of age,
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Given signed, written informed consent
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Existence of at least one measurable tumor lesion by CT or MRI at the time of treatment, but no single lesion ≥ 8 cm in diameter.
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At least 4 weeks recovery period after any major surgery, radiation, or chemotherapy, and total recovery from any acute toxicities associated with these prior treatments.
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Life expectancy ≥ 3 months, Karnofsky performance status of ≥ 70%
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Adequate hematology and renal function and hepatic function
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Patients of childbearing potential must be willing to practice birth control during the study until at least 12 weeks after treatment, and women of childbearing potential must have a negative serum pregnancy test to enter the study
Exclusion Criteria :
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Known central nervous system metastatic disease
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25% bone marrow involvement
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CEA plasma levels >2,000 ng/mL
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Patients with successfully treated non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
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HIV positive, hepatitis B-antigen positive, or hepatitis C positive patients
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Known autoimmune disease,
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Known history of unstable angina, myocardial infarction, or congestive heart failure present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy, no known history of clinical significant, active chronic obstructive pulmonary disease, or other moderate to severe chronic respiratory illness present within 6 months
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Infection requiring intravenous antibiotic use within 1 week before inclusion,
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Corticosteroids are not allowed within 2 weeks of study entry nor during the study except low doses (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illness such as rheumatoid arthritis.
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Patients who received a treatment containing a nitrosourea compound will not be enrolled for at least 6 weeks after the end of that treatment.
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Known hypersensitivity to murine antibodies or proteins
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Immunization against TF2 for patients who has already received injection of TF2
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Adult patient unable to give informed consent because of intellectual impairment.
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Adult patient protected by the French law
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | CHU de Nantes | Nantes | France | 44093 |
Sponsors and Collaborators
- Nantes University Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RC14_0003