ImmunoTEP au 68-Ga- IMP-288 for Patients With a Recurrence of HER2 Negative Breast Carcinoma Expressing CEA (iTEPsein)

Pilot Study for Optimization of Immuno-PET Pretargeted With Anti-CEA Bispecific Antibody X Anti-HSG TF2 and the Peptide IMP-288 Radiolabeled With Gallium-68 -Pharmacokinetic and Imaging for Patients With a Recurrence of HER2 Negative Breast Carcinoma Expressing CEA

Main objective: To determine the optimal molar doses of the biospecific antibody TF2 and 68 Ga-IMP-288 and the optimal time for pretargeting for immuno-PET in patients with breast carcinoma.

Secondary objectives: To study the sensitivity of the immuno-PET, compare its performance to standard imaging methods, evaluate the safety of 150 MBq of 68 Ga-IMP-288; study the development of immunization against TF2 or complex TF2-IMP-288;

Study Overview

• Status: Completed
• Conditions: HER2 Negative Breast Carcinoma Expressing CEA
• Intervention / Treatment: Drug: TF2 - 68 Ga-IMP-288:

Detailed Description

• 4 or 5 cohorts of 3 patients receiving different doses of TF2 IMP-288 with different interval time. A last cohort (4 or 5 ): maximum of 21 additional patients with the optimal schedule.

Cohort I: TF2 120 nmol / 6 nmol IMP-288 / 24 hours

Cohort II: based on the results of the cohort I :

1. Good signal of the tumor but high background: increased interval time, 120 nmol TF2 / 6 nmol of IMP-288 / 30 hours
2. Low signal of the tumor: reduction of the interval time, 120 nmol TF2 / 6 nmol IMP-288 / 18 hours

3. Good signal of the tumor and good background signal : dose reduction, 60 nmol TF2 / 3nmol IMP- 288 / 24 hours

   Cohort III: based on results of cohort II:

   - Good signal of the tumor : dose reduction, 120 nmol TF2 / 3 nmol IMP-288 / 30 h

   Cohort IV : based on results of cohort III Cohort V : Based on results of cohort IV

   • A last Cohort (VI) : 19 patients with the optimal schedule of injection : 120 nmol TF2 / 3 nmol IMP-288 / 30 h or 120 nmol TF2 / 6 nmol IMP-288 / 30 h

   • In the four weeks prior to the immuno-PET:

   - Clinical examination,

   - CEA and CA15-3,

   - thoraco abdominal pelvic scan, bone scan, FDG-PET,

   - immunohistochemistry ACE on the tumor if possible,

   - Anti-Antibodies if the patient has already received MAb,

   - pregnancy test within 2 days prior to immuno-PET,

   - (creatinine > 2.5 normal) D0: Injection of TF2 D1 to D4: injection of 68 Ga-IMP-288 (depending of the cohort) D0 to D4 : pharmacokinetics, imaging

   Evaluation at 1 month of Immuno-PET:

   • Assessment of the clinical oncologist and

   - histological biopsy and / or surgery performed according to the results of imaging and assessment of the potential clinical impact

   Evaluation at 3 and 6 months of immuno-PET:

   based on the results of immuno-PET, evaluation and therapeutic decision of the oncologist,

   - Imaging (ultrasound, bone scintigraphy, CT or PET FDG),

   - markers

   • Anti-Antibody Search
   • For patient with a cancer treatment a new immuno-PET can be proposed

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Hospital
  • Saint Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Breast carcinoma, HER2 + (Dako) and HER2 + (fish) metastatic at least after treatment with current consensus
• ≥ 18 years
• Negative pregnancy test for women of childbearing age. Women of childbearing age should take effective contraception continuously for 3 months.

• Karnofsky ≥ 70 or ECOG 0-1

  •• ACE of the tumor by immunohistochemistry or positive plasma CEA ≥ 10 ng / mL

• At least one measurable lesion on CT
• creatinine < 2.5
• Informed consent signed
• Social insurance

Exclusion Criteria:

• Pregnancy or breastfeeding

  • Serious illness or co-morbidity risk assessed
  • History of cancer within 5 years except skin cancer other than melanoma or carcinoma in situ of the cervix
  • Presence of anti-antibodies in patients who have previously received antibodies
  • Known hypersensitivity to antibodies or proteins
  • intellectual disability to sign the informed consent
  • Not controlled diabetes
  • Persons protected by law

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of the tumor targeting (no Unit) and signal / noise ratio (no unit) by the immunoTEP with TF2 and 68-Ga-IMP-288	Pk blood after injections of TF2 and 68 Ga-IMP-288 and PET imaging semi-quantification with 60 to 120 minutes after injection of 68 Ga-IMP-288	One week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensibility, tolerance	sensitivity of the immuno-PET and compare its performance to standard imaging methods, pathological data if available data or imaging follow-up of at least 6 months by RECIST and EORTC	6 months after immunoTEP
To study the contribution of immnoTEP to assess early response to treatment, compare its performance to standard imaging methods	6 weeks after initiation of treatment of metastases (after the first iTEP), a second _iTEP with a therapeutic evaluation will be carried out. The examination requirements are identical to those of the first immunoTEP. this second iITEP will be evaluated in regard of imaging assessment performed routinely (TAP scanner, FDG-PET, CA15-3 and CEA)	month 6

Other Outcome Measures

Outcome Measure	Time Frame
• To assess the tolerance of 150 MBq of 68 Ga-IMP-288	6 months
To search for the development of immunization with TF2 and the complex TF2-IMP-288: ELISA	6 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Gilead Sciences
• Investigators: Principal Investigator: francoise Bodere, PhD, MD, Nantes Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: November 12, 2012
• First Submitted That Met QC Criteria: November 20, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2 negative; ImmunoTEP
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Breast Diseases; Breast Neoplasms; Carcinoma; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Glycine Agents; Histamine Agonists; Glycine; Histamine
• Other Study ID Numbers: BRD/10/04-O