Clinical trial NCT01805908: 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)
Official title: Imaging With 111In-Pertuzumab to Predict Response to Trastuzumab in HER2 Positive Metastatic or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: metastatic
breast cancer
herceptin
imaging
tumour response
adenocarcinoma
SPECT-CT
pertuzumab
trastuzumab
locally advanced
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
First posted: 2013-03-06
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in tumour SUV (Standardized Uptake Value) from baseline to Day 8.
timeFrame: 8 days
measure: Safety attributable to 111In-Pertuzumab injections
timeFrame: 3 months
Secondary outcomes:
measure: Pharmacokinetics (PK) and tumour and normal tissue localization properties of 111In-PmAb will be measured.
timeFrame: 3 months
measure: Optimal mass dose of 111In-PmAb
timeFrame: 3 months
measure: Change in tumour SUV from Baseline to Day 36
timeFrame: 3 months
measure: Clinical response (complete or partial) to treatment will be measured using Response Evaluation Criteria In Solid Tumours (RECIST) criteria.
timeFrame: 3 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
Study officials:
affiliation: Ontario Clinical Oncology Group, McMaster University
name: Mark Levine
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto
name: Raymond Reilly
role: PRINCIPAL_INVESTIGATOR
affiliation: Ontario Clinical Oncology Group (OCOG)
name: Kathleen Pritchard
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.