Pretargeted Radioimmunotherapy in Metastatic Colorectal Cancer (RITCOLON)

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

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).

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Antibody TF2; Drug: 90-Y-IMP-288; Drug: 111-In-IMP-288

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Elevated CEA serum level or proved CEA expression in tumor tissue
3. ≥ 18 years of age,
4. Given signed, written informed consent
5. 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.
6. 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.
7. Life expectancy ≥ 3 months, Karnofsky performance status of ≥ 70%
8. Adequate hematology and renal function and hepatic function
9. 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 :

1. Known central nervous system metastatic disease
2. > 25% bone marrow involvement
3. CEA plasma levels >2,000 ng/mL
4. 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.
5. HIV positive, hepatitis B-antigen positive, or hepatitis C positive patients
6. Known autoimmune disease,
7. 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
8. Infection requiring intravenous antibiotic use within 1 week before inclusion,
9. 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.
10. Patients who received a treatment containing a nitrosourea compound will not be enrolled for at least 6 weeks after the end of that treatment.
11. Known hypersensitivity to murine antibodies or proteins
12. Immunization against TF2 for patients who has already received injection of TF2
13. Adult patient unable to give informed consent because of intellectual impairment.

14. Adult patient protected by the French law

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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)

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2015
• Primary Completion (Actual): September 20, 2017
• Study Completion (Actual): December 20, 2017

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Actual): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: RC14_0003