Pretargeted Radioimmunotherapy in Metastatic Colorectal Cancer

Study Overview
=================
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).

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.

Official Title
-----------------
Pretargeted Radioimmunotherapy in Metastatic Colorectal Cancer : A Multicentric Phase I/II Study of Fractionated TF2 Plus 90Y-IMP288 (RITCOLON)

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Antibody TF2
* Drug: 90-Y-IMP-288
* Drug: 111-In-IMP-288


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Elevated CEA serum level or proved CEA expression in tumor tissue ≥ 18 years of age, Given signed, written informed consent 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. 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. Life expectancy ≥ 3 months, Karnofsky performance status of ≥ 70% Adequate hematology and renal function and hepatic function 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 : Known central nervous system metastatic disease > 25% bone marrow involvement CEA plasma levels >2,000 ng/mL 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. HIV positive, hepatitis B-antigen positive, or hepatitis C positive patients Known autoimmune disease, 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 Infection requiring intravenous antibiotic use within 1 week before inclusion, 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. Patients who received a treatment containing a nitrosourea compound will not be enrolled for at least 6 weeks after the end of that treatment. Known hypersensitivity to murine antibodies or proteins Immunization against TF2 for patients who has already received injection of TF2 Adult patient unable to give informed consent because of intellectual impairment. Adult patient protected by the French law -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: several cohorts<br>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<br>* injection of a recombinant antibody CEA specific. Three injections. Each injection are separate by one week<br>Drug: 90-Y-IMP-288<br>* 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)<br>Drug: 111-In-IMP-288<br>* Injection of the peptide 111-In-IMP-288, 24 Hours after the first injection of TF2 (week 1)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose for 90Y-IMP288. | toxicity analysis | Week 6 to week 12 |