HER2 Negative Breast Carcinoma Expressing CEA
Conditions
Keywords
ImmunoTEP, HER2 negative, Breast Cancer
Brief summary
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;
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
Interventions
DRUGTF2 - 68 Ga-IMP-288:
ImmunoTEP
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Gilead Sciences
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| evaluation of the tumor targeting (no Unit) and signal / noise ratio (no unit) by the immunoTEP with TF2 and 68-Ga-IMP-288 | One week | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To study the contribution of immnoTEP to assess early response to treatment, compare its performance to standard imaging methods | month 6 | 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) |
| Sensibility, tolerance | 6 months after immunoTEP | 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 |
Other
| 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 |
Countries
France
Outcome results
None listed