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)

Phase 1

Terminated

• Conditions: Breast Cancer
• Interventions: Other: 111In-Pertuzumab + SPECT-CT

• Registration Number: NCT01805908
• Lead Sponsor: Ontario Clinical Oncology Group (OCOG)

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-02-12
• Study First Submitted QC: 2013-03-05
• Study First Posted: 2013-03-06
• Study Start: 2013-11
• Status Verified: 2016-06
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Last Update Submitted: 2016-06-03
• Last Update Posted: 2016-06-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 3

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
111In-Pertuzumab + SPECT-CT	111In-Pertuzumab + SPECT-CT	Radiopharmaceutical 111In-labeled Pertuzumab given intravenously prior to SPECT-CT imaging.

Primary Outcome Measures

Name	Time	Method
Change in tumour SUV (Standardized Uptake Value) from baseline to Day 8.	8 days	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.
Safety attributable to 111In-Pertuzumab injections	3 months	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.

Secondary Outcome Measures

Name	Time	Method
Optimal mass dose of 111In-PmAb	3 months	The dose of 111In-PmAb that is associated with the optimal SPECT-CT images will be established.
Pharmacokinetics (PK) and tumour and normal tissue localization properties of 111In-PmAb will be measured.	3 months	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.
Clinical response (complete or partial) to treatment will be measured using Response Evaluation Criteria In Solid Tumours (RECIST) criteria.	3 months	Clinical response (complete or partial) to treatment will be measured using Response Evaluation Criteria In Solid Tumours (RECIST) criteria.
Change in tumour SUV from Baseline to Day 36	3 months	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.

Trial Locations

Locations (2)

Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

Sunnybrook Odette Cancer Centre; 🇨🇦 Toronto, Ontario, Canada