Clinical trial NCT03924466: Repeatability of 68-GaNOTA-Anti-HER2 VHH1 PET/CT in Breast Carcinoma Patients
Official title: Quantification of 68-GaNOTA-Anti-HER2 VHH1 Uptake in Metastasis of Breast Carcinoma Patients and Assessment of Repeatability (VUBAR) - Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Carcinoma
Locally Advanced Breast Cancer
Cancer of Pancreas
Solid Tumor With Intermediate or High HER2 Expression
Salivary Gland Cancer
Gastric Cancer
Endometrial Cancer
Uterine Cancer
Non Small Cell Lung Cancer
Biliary Tract Cancer
Cholangiocarcinoma
Colorectal Cancer
Urothelial Carcinoma
Prostate Cancer
Keywords: HER2
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
name: Agentschap voor Innovatie door Wetenschap en Technologie, Project Toegepast Biomedisch onderzoek met een primair Maatschappelijke finaliteit.
First posted: 2019-04-23
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The trial consists of 3 different patient cohorts that are each investigated using a new diagnostic imaging radiopharmaceutical
Primary purpose: DIAGNOSTIC

Brief summary: Study objective:

Cohort 1: To quantify the uptake of 68GaNOTA-Anti-HER2 VHH1 in local or distant metastases from breast carcinoma patients and to assess repeatability of the image-based HER2 quantification. The uptake will be correlated to results obtained via biopsy of the same lesion, if available.

Cohort 2: To report on uptake of 68GaNOTA-Anti-HER2 VHH1 in different cancer types that might overexpress HER2

Cohort 3: To explore the feasibility and added value of 68GaNOTA-Anti-HER2 VHH1 in the neoadjuvant setting of HER2-expressing breast carcinoma

Time schedule: After inclusion, patients will be injected intravenously with 37 - 185 MBq 68GaNOTA-Anti-HER2 VHH1 with a total mass of up to 200 μg NOTA-Anti-HER2 VHH1. Serum and plasma samples will be collected at injection. At 90 min after injection, a total body PET/CT scan will be performed.

Patients in cohort 1 will undergo a second PET/CT procedure, identical to the first procedure, within 8 days, with a minimal interval of 18h and maximal interval of 8 days. Patients in cohort 2 can undergo an optional 18F-FDG-PET/CT within 21 days prior to or after 68GaNOTA-Anti-HER2 VHH1. In cohort 1 and 2, based on PET/CT images, up to 2 lesions will be selected for optional image-guided biopsy. Biopsy will be performed max. 28 days after the last PET/CT. Plasma and serum samples will be obtained between 60 and 365 days after first injection for patients in cohort 1 and between 42 and 365 days after first injection for patients in cohort 2.

Patients in cohort 3 will undergo 68GaNOTA-Anti-HER2 VHH1 PET/CT prior to the start of neoadjuvant treatment and again after the last cycle of neoadjuvant treatment but prior to surgery. Plasma and serum samples will be obtained before each injection and between 42 and 365 days after the last injection.


Eligibility criteria: COHORT SPECIFIC INCLUSION CRITERIA:

COHORT 1:

Patients will only be included in the study if they meet all of the following criteria:

* Patient who has given informed consent
* Patient with age 18 years or older
* Patient with locally or distantly advanced breast carcinoma, with at least 1 lesion of at least 12 mm maximal diameter. For lymph node metastases, the largest diameter should be at least 15 mm and the short axis at least 12 mm.

COHORT 2:

Patients will only be included in the study if they meet all of the following criteria:

* Patient who has given informed consent
* Patient with age 18 years or older
* Patients with locally advanced, unresectable, or metastatic cancer disease , with at least 1 lesion of at least 10 mm maximal diameter (For lymph node metastases, short axis at least 10 mm) of any of the following types:

  * breast carcinoma with low, intermediate or high HER2-expression, based on IHC 1+ or IHC 2+ or IHC 3+, as determined by local assessment on any of the available cancer tissues
  * salivary gland cancer
  * adenocarcinoma of the gastric body or gastro-esophageal junction
  * endometrial cancer
  * cancer of cervix uteri
  * Non-small cell lung cancer
  * biliary tract cancer including intra- or extrahepatic cholangiocarcinoma and tumors arising in the ampulla of Vater or gallbladder.
  * pancreatic cancer
  * colorectal cancer
  * urothelial carcinoma, including transitional cell or predominantly transitional cell carcinoma of the renal pelvis, ureter, urinary bladder or urethra.
  * prostate cancer
  * Other solid malignant tumors with intermediate or high HER2-expression, based on IHC 2+ or IHC 3+, as determined by local assessment on any of the available cancer tissues
* Patients who have progressed following at least one prior systemic treatment for metastatic or advanced disease, or who have no satisfactory alternative treatment option, according to the treating physician (based on all available data such as medical imaging, lab results, clinical examination, ...), and who are considered for a next line of systemic treatment. Patients who already participated in the trial and who are diagnosed with progressive or recurrent disease can be re-included if all inclusion criteria and none of the exclusion criteria apply.

COHORT 3:

Patients will only be included in the study if they meet all of the following criteria:

* Patient who has given informed consent
* Patient with age 18 years or older
* Patient with local or locally advanced HER2-positive (either IHC 3+ and/or ISH positive) breast carcinoma, who is planned for neo-adjuvant treatment prior to surgery, and who is suspected for axillary lymph node invasion, based on clinical assessment, ultrasound, CT or MRI, or who has a confirmed lymph node invasion
* Patients who either had 18F-FDG- PET/CT in the last 4 weeks before inclusion, or for whom 18F-FDG- PET/CT is planned before start of neoadjuvant treatment.

GENERAL EXCLUSION CRITERIA:

Patients will not be included in the study if one or more of the following criteria applies:

* Patient is pregnant
* Patient is breast feeding
* Patient with recent (\< 1 week) gastrointestinal disorders with diarrhea as major symptom
* Patient with any serious active infection
* Patient who has any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the test radiopharmaceutical
* Patient who cannot communicate reliably with the investigator
* Patient who is unlikely to cooperate with the requirements of the study
* Patient who is unwilling and/or unable to give informed consent
* Patient at increased risk of death from a pre-existing concurrent illness

COHORT SPECIFIC EXCLUSION CRITERIA

COHORT 1 \& 3:

* Patient who participated already in this study

Primary outcomes:
measure: Repeatability of lesional PET/CT characteristics
timeFrame: 90 min post injection
measure: Tracer update of 68GaNOTA-Anti-HER2 VHH1 in different cancer types
timeFrame: 90 min post injection
measure: Feasibility and added value of 68GaNOTA-Anti-HER2 in neoadjuvant setting of breast carcinoma
timeFrame: time of surgery following neo-adjuvant treatment (typically within 14 days following the second intervention)
Secondary outcomes:
measure: Within-patient tumor heterogeneity for HER2 expression using PET/CT imaging
timeFrame: 90 min post injection
measure: Immunogenicity
timeFrame: prior to and between 60 and 365 days after the first injection
measure: Histopathological results of biopsied lesions and correlation with PET/CT results
timeFrame: max 28 days after the second PET/CT
measure: Influence image-guide biopsy on patient management
timeFrame: Within 3 months following the last intervention
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Uz Brussel
state: Brussel
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Marleen KEYAERTS, MD
role: PRINCIPAL_INVESTIGATOR
References: