Safety and Efficacy of Ga68-IAC PET/CT for Diagnosis and Clinical Management in Metastatic Breast Cancer Patients

Official title

Safety and Efficacy of Ga-68-IAC Positron Emission Tomography (PET/CT) for Diagnosis and Clinical Management in Metastatic Breast Cancer Patients.

Overview

This is a phase I/IIa, open label, multicenter interventional study of Gallium-68 radiolabeled Integrin Adhesion Complex antagonist conjugate (Ga-68-IAC) Positron Emission Tomography (PET/CT) imaging, intended for diagnosis, and clinical management of patients with Metastatic 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-IAC PET/CT 2-5 mCi to evaluate safety, biodistribution, and response to treatment in metastatic breast cancer patients.

Interventions

• Diagnostic test Ga-68-IAC
  Clinical management and diagnosis of Metastatic Breast Cancer.

Primary outcome measures

• Specific Aims 1:To evaluate the safety, toxicity profile and tolerability of Ga-68-IAC in patients diagnosed with angiogenic breast cancer. [Time frame: 6 Months]
• Specific Aims 2:To evaluate biodistribution and dosimetry of Ga-68-IAC [Time frame: 6 Months]
• Specific Aims 3: To determine the recommended phase 2 dose (RP2D) of Ga-68-IAC examination [Time frame: 6 Months]

Secondary outcome measures (1)

• Specific Aim 1: To determine the pharmacokinetic and pharmacodynamic profile of Ga-68-IAC [Time frame: 6 Months]

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:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Hemoglobin (Hb) ≥9 g/dl (transfusion or use of EPO is permitted).
• Platelets > 100,000/mm3
• Creatinine ≤ 1.5 x normal value based on the Cock Gault (CG) equation.
• AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)
• 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.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

India · 2 centers

• Postgraduate Institute of Medical and Research — Chandigarh
• All India Institute of Medical Sciences — New Delhi

South Africa · 1 center

• University of Witwatersrand — Johannesburg

Publications

• 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. PMID 25945808
• 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. PMID 22853992

Identifiers

NCT: NCT04480619 · 145314

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗