Imaging With 111 Indium (111In)-Pertuzumab (PmAb) to Predict Response to Trastuzumab (TmAb) in Human Epidermal Growth Factor-2 (HER2) Positive Metastatic Breast Cancer (MBC) or Locally Advanced Breast Cancer (LABC) (PETRA)

Imaging With 111In-Pertuzumab to Predict Response to Trastuzumab in HER2 Positive Metastatic or Locally Advanced Breast Cancer

The general objective of the study is to improve the care of women with Human Epidermal Growth Factor Receptor-2 (HER2) positive metastatic or locally advanced breast cancer by using a radio-labelled biomarker with whole body Single Photon Emission Computed Tomography (SPECT) imaging to predict who will respond to treatment with Trastuzumab.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Other: 111In-Pertuzumab + SPECT-CT

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Juravinski Cancer Centre
    • Toronto, Ontario, Canada
      • Sunnybrook Odette Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Metastatic, locally recurrent (local recurrence not amenable to surgical resection of curative intent), or locally advanced (T3 or T4, any N, M0) adenocarcinoma of the breast.
2. Tumour HER2 positive by immunohistochemistry for HER2 protein over-expression or by Fluorescence in situ Hybridization (FISH) for HER2 gene amplification, as defined by American Society of Clinical Oncology/College of American Pathologists guidelines
3. Initiating treatment with TmAb
4. Clinically measurable disease (by RECIST for patients with metastatic disease).

Exclusion Criteria:

1. Male gender.
2. Less than 18 years of age.
3. Life expectancy < 12 weeks.
4. Only site of metastases is liver.
5. Eastern Cooperative Oncology Group (ECOG) performance status of > 2.
6. Currently receiving PmAb or lapatinib for treatment of MBC.
7. Having received TmAb as adjuvant therapy within the previous 6 months.
8. Required to receive another radiopharmaceutical during the first week of the study.
9. Hypersensitivity to monoclonal antibodies.
10. Left Ventricular Ejection Fraction (LVEF) < 50% at baseline (within 42 days of study registration) as determined by either echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) scan.

11. Hematology and/or biochemistry parameters outside acceptable ranges:

    • absolute neutrophil count <1,500 cells/mm3,
    • platelet count <100,000 cells/mm3,
    • hemoglobin <9 g/dL,
    • total bilirubin > upper limit of normal (ULN) (unless subject has documented Gilbert's Syndrome),
    • aspartate aminotransferase (AST) [serum glutamic oxaloacetic transaminase(SGOT)] and alanine aminotransferase (ALT) [serum glutamic pyruvate transaminase(SGPT)] >2.5 × ULN,
    • serum creatinine >2.0 mg/dL or 177 μmol/L,
    • alanine aminotransferase (ALP) >2.5 x ULN.
12. Known pregnancy or lactating female (e.g. positive serum beta-human chorionic gonadotropin (B-hCG) pregnancy test).
13. For women of childbearing potential, failure to agree to use a highly effective form of contraception (patient and/or partner, e.g., surgical sterilization) or two effective forms of contraception (a reliable barrier method in conjunction with spermicidal jelly, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of study treatment.
14. Any condition, which in the investigator's opinion would not make the patient a suitable candidate for inclusion in the trial.
15. Participation in another clinical trial.
16. Inability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 111In-Pertuzumab + SPECT-CT; Radiopharmaceutical 111In-labeled Pertuzumab given intravenously prior to SPECT-CT imaging.	Other: 111In-Pertuzumab + SPECT-CT; 111In-PmAb will be provided ready for injection in a vial by Dr. Reilly's laboratory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tumour SUV (Standardized Uptake Value) from baseline to Day 8.	The imaging outcome for exploring the association between imaging and clinical outcome is the percent change in tumour SUV from baseline to Day 8 (Day 8 SUV - baseline SUV) /baseline SUV times 100%. The Positron Emission Tomography Evaluation Response Criteria In Solid Tumours (PERCIST) criterion will be used to measure SUV change.	8 days
Safety attributable to 111In-Pertuzumab injections	The safety, i.e. toxicities, attributable to 111In-Pertuzumab injections will be evaluated using the National Cancer Institute (NCI) Common Termination for Adverse Events Version 4.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) and tumour and normal tissue localization properties of 111In-PmAb will be measured.	The pharmacokinetics of 111In-PmAb and tumour and normal tissue localization properties of 111In-PmAb will be measured. Standard PK parameters (t1/2 alpha, t1/2β, V1, Vss and CL) will be calculated.	3 months
Optimal mass dose of 111In-PmAb	The dose of 111In-PmAb that is associated with the optimal SPECT-CT images will be established.	3 months
Change in tumour SUV from Baseline to Day 36	The imaging outcome for exploring the association between imaging and clinical outcome is the percent change in tumour SUV from baseline to Day 36 (Day 36 SUV - baseline SUV) /baseline SUV times 100%. The Positron Emission Tomography Evaluation Response Criteria In Solid Tumours (PERCIST) criterion will be used to measure SUV change.	3 months
Clinical response (complete or partial) to treatment will be measured using Response Evaluation Criteria In Solid Tumours (RECIST) criteria.	Clinical response (complete or partial) to treatment will be measured using Response Evaluation Criteria In Solid Tumours (RECIST) criteria.	3 months

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Investigators: Principal Investigator: Mark Levine, Ontario Clinical Oncology Group, McMaster University; Principal Investigator: Raymond Reilly, University of Toronto; Principal Investigator: Kathleen Pritchard, Ontario Clinical Oncology Group (OCOG)

Publications and helpful links

General Publications

• Lam K, Chan C, Done SJ, Levine MN, Reilly RM. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of (111)In-BzDTPA-pertuzumab. Nucl Med Biol. 2015 Feb;42(2):78-84. doi: 10.1016/j.nucmedbio.2014.09.011. Epub 2014 Oct 14.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: February 12, 2013
• First Submitted That Met QC Criteria: March 5, 2013
• First Posted (Estimate): March 6, 2013

Study Record Updates

• Last Update Posted (Estimate): June 6, 2016
• Last Update Submitted That Met QC Criteria: June 3, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: breast cancer; imaging; trastuzumab; metastatic; adenocarcinoma; herceptin; tumour response; SPECT-CT; pertuzumab; locally advanced
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pertuzumab
• Other Study ID Numbers: OCOG-2011-PETRA