Clinical trial NCT04480619: Safety and Efficacy of Ga68 Αvβ3 IAC PET/CT for Diagnosis and Clinical Management in Angiogenic Breast Cancer Patients
Official title: Safety and Efficacy of Ga-68-Αvβ3 IAC Positron Emission Tomography (PET/CT) for Diagnosis and Clinical Management in Angiogenic Breast Cancer Patients.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Angiogenic Breast Cancer
Lead sponsor: Advanced Imaging Projects, LLC
Sponsor class: INDUSTRY
Collaborators: name: All India Institute of Medical Sciences
name: Post Graduate Institute of Medical Education and Research, Chandigarh
name: University of Witwatersrand, South Africa
name: US Department of Veterans Affairs
First posted: 2020-07-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Ga-68 PEG-Αvβ3-IAC PET/CT
Primary purpose: DIAGNOSTIC

Brief summary: This is a phase I/IIa, open label, multicenter interventional study of Gallium-68 radiolabeled PEG-αvβ3-Integrin Adhesion Complex antagonist conjugate (Ga-68-PEG-Αvβ3-IAC) Positron Emission Tomography (PET/CT) imaging, intended for diagnosis, and clinical management of patients with angiogenic breast cancer.

Detailed description: This is a prospective non blinded trial, Phase I/IIa, multicenter, study in a total of up to 25 subjects with angiogenic therapy indication for breast cancer. All patients with confirmed diagnoses will undergo \[18F\]Fluoro-deoxyglucose (18F-FDG) PET/CT (6-12 mCi) and Ga-68-PEG-αvβ3 IAC PET/CT 2-5 mCi to evaluate safety, biodistribution, and response to treatment in angiogenic breast cancer patients.

Eligibility criteria: Inclusion Criteria:

* Patients with solid tumors (either 3+ by immunohistochemistry or with evidence of gene amplification (\>2.0) by fluorescence in situ hybridization (FISH))

  * At least 18 years of age
  * Able to provide informed consent.

Karnofsky score greater than 50

* Females of childbearing potential must have a negative pregnancy test at screening/baseline
* AIP-301 Ga-68 positive scan define by SUV greater than 10.
* Adequate organ function, defined as:

  1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
  2. Hemoglobin (Hb) ≥9 g/dl (transfusion or use of EPO is permitted).
  3. Platelets \> 100,000/mm3
  4. Creatinine ≤ 1.5 x normal value based on the Cock Gault (CG) equation.
  5. AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)
  6. Alkaline phosphatase ≤2.5 x ULN. Alkaline phosphatase may be more than 2.5 x ULN only in the case of bone metastases, and AST and ALT less than 1.5 x ULN.
  7. Total bilirubin ≤1.5 mg/dl (higher bilirubin levels are permitted if the patient has Gilbert's syndrome).

Baseline LVEF ≥50% measured using echocardiogram or equilibrium

isotopic ventriculography (MUGA).

Exclusion Criteria:

* • Serum creatinine \>3.0 mg/dL (270 μM/L)

  * Hepatic enzyme levels more than 5 times upper limit of normal.
  * Known severe allergy or hypersensitivity to IV radiographic contrast.
  * Use of any other investigational product or device within 30 days prior to dosing or known requirement for any other investigational agent prior to completion of all scheduled study assessments.
  * Patients with a body weight of 400 pounds or more or not able to enter the bore of the PET/CT scanner due to BMI, because of the compromise in image quality with CT, PET/CT and MRI that will result.
  * Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.).
  * Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.)
  * Recognized concurrent active infection (e.g., HIV)
  * Previous Grade 3 or higher allergic reaction to Trastuzumab that resulted in discontinuation of Trastuzumab therapy. Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance.

    * Adult patients who require monitored anesthesia for PET scanning

Primary outcomes:
measure: Specific Aims 1:To evaluate the safety, toxicity profile and tolerability of Ga-68-PEG-αvβ3-IAC in patients diagnosed with angiogenic breast cancer.
timeFrame: 6 Months
measure: Specific Aims 2:To evaluate biodistribution and dosimetry of Ga-68-PEG-αvβ3-IAC
timeFrame: 6 Months
measure: Specific Aims 3: To determine the recommended phase 2 dose (RP2D) of Ga-68-PEG-αvβ3-IAC examination
timeFrame: 6 Months
Secondary outcomes:
measure: Specific Aim 1: To determine the pharmacokinetic and pharmacodynamic profile of Ga-68-PEG-αvβ3-IAC
timeFrame: 6 Months
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical and Research
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Johannesburg
country: South Africa
facility: University of Witwatersrand
Study officials:
References:
citation: Baum RP, Kulkarni HR, Muller D, Satz S, Danthi N, Kim YS, Brechbiel MW. First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for alphavbeta3 Integrin Receptor Targeting. Cancer Biother Radiopharm. 2015 May;30(4):152-9. doi: 10.1089/cbr.2014.1747.
citation: Kim YS, Nwe K, Milenic DE, Brechbiel MW, Satz S, Baidoo KE. Synthesis and characterization of alphavbeta(3)-targeting peptidomimetic chelate conjugates for PET and SPECT imaging. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5517-22. doi: 10.1016/j.bmcl.2012.07.024. Epub 2012 Jul 14.