Clinical trial NCT01730612: ImmunoTEP au 68-Ga- IMP-288 for Patients With a Recurrence of HER2 Negative Breast Carcinoma Expressing CEA
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HER2 Negative Breast Carcinoma Expressing CEA
Keywords: ImmunoTEP
HER2 negative
Breast Cancer
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Gilead Sciences
First posted: 2012-11-21
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

Eligibility criteria: 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

Primary outcomes:
measure: evaluation of the tumor targeting (no Unit) and signal / noise ratio (no unit) by the immunoTEP with TF2 and 68-Ga-IMP-288
timeFrame: One week
Secondary outcomes:
measure: Sensibility, tolerance
timeFrame: 6 months after immunoTEP
measure: To study the contribution of immnoTEP to assess early response to treatment, compare its performance to standard imaging methods
timeFrame: month 6
Other outcomes:
measure: • To assess the tolerance of 150 MBq of 68 Ga-IMP-288
timeFrame: 6 months
measure: To search for the development of immunization with TF2 and the complex TF2-IMP-288: ELISA
timeFrame: 6 months
Locations:
city: Nantes
country: France
facility: Hospital
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
Study officials:
affiliation: Nantes Hospital
name: francoise Bodere, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: