Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Estrogens

Jeffrey Vacirca, MD

This multicenter, prospectively designed study examines whether the Prosigna score influences physician and patient adjuvant treatment selection over and above currently used prognostic factors. This study also examines the impact of the test results on patients' reported outcomes, including their decisional conflict status and anxiety levels.

The primary objective of this study is to assess the extent to which the Prosigna test results affect the medical oncologist's treatment recommendations regarding adjuvant chemotherapy and actual treatments received for patients with early stage breast cancer conventionally considered candidates for genomic testing based on current treatment guidelines. The oncologist's initial recommendations will be based on the utilization of tools or algorithms based on clinical and pathologic factors. No genomic tools will be used in the initial assessment. Changes in recommendation after availability of Prosigna test results will include (1) hormonal therapy alone or (2) hormonal therapy plus chemotherapy, and (3) changes in types of chemotherapy if chemotherapy was recommended before and after the test.

Prospective Observational Study Evaluating Treatment Decision Impact of Prosigna® in Early Stage Breast Cancer Patients

A Prospective Observational Study Evaluating Treatment Decision Impact of Prosigna® in Early Stage Breast Cancer Patients Who Are Candidates for Genomic Testing

NanoString Technologies, Inc.

Miguel Martin, M.D., Ph.D.

The primary objective of this study is to assess the extent to which the Prosigna™ Breast Cancer Prognostic Gene Signature Assay affects the medical oncologist's treatment recommendations regarding adjuvant chemotherapy and actual treatments received for patients with early-stage breast cancer.

Changes in treatment recommendations will include (1) hormonal therapy alone, (2) hormonal therapy plus chemotherapy, and (3) changes in types of chemotherapy if chemotherapy was recommended before and after the Prosigna test.

A Prospective Observational Study of Clinical Outcomes for the NanoString® Technologies Prosigna Gene Signature Assay

Prospective Observational Study to Evaluate the Impact of the Determination of the Intrinsic Subtypes of Breast Cancer by PAM50 NanoString Technology in the Use of Adjuvant Chemotherapy in Women With Breast Cancer, HR+ and Node -.

Cedar Associates LLC

Illumina, Inc.

Grupo Espanol de Investigacion del Cancer de Mama

Spanish Breast Cancer Research Group

Hospital General Universitario Gregorio Marañon

Vall d'Hebron Institute of Oncology

Antineoplastic Agents

Herbal and Botanical

Amino Acids

Trastuzumab

Hormones

Exemestane

Letrozole

Anastrozole

Aromatase Inhibitors

Lapatinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Orange

Tyrosine

In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.

In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

Lapatinib is available as 250-mg orange tablets. Subjects randomized to the Lapatinib plus Trastuzumab arm received 1000 mg per day of Lapatinib, so wre instructed to take 4 x 250 mg tablets per day. Lapatinib was to be taken either 1 hour (or more) before a meal or 1 hour (or more) after a meal

Trastuzumab is a sterile, white to pale yellow, preservative-free lyophilized powder for IV administration. Trastuzumab was administered on Day 1 of the start of Lapatinib or in conjunction with the first cycle of chemotherapy, as an 8 mg/kg loading dose. Subsequently, Trastuzumab was administered q3weekly as a 6 mg/kg maintenance dose. At the discretion of the investigator, weekly Trastuzumab could be given in either of the three treatment arms (loading dose 4mg/kg followed by weekly administration of 2mg/kg).

Subjects who were hormone receptor-positive were required to receive an aromatase inhibitor as combination treatment; however the choice of the aromatase inhibitor selected for each patient was determined by the patients' investigator. The AIs the Investigator could choose from were anastrozole, exemestane, and letrozole and dosing was per product information.

Aromatase Inhibitors (AIs)

Novartis Pharmaceuticals

This was a multicenter, open-label, Phase II study in subjects with Human epidermal growth factor receptor (HER2)-positive metastatic breast cancer who received at least 2 prior lines of anti-HER2-targeted therapies of which at least one included a Trastuzumab-containing regimen. This study was a post-approval commitment with regulatory authorities. It was designed to evaluate whether treatment with Dual blockade promoted changes to biomarkers associated with immunomodulation.

This study was designed to address the post-authorization measures as agreed with the Committee for Medicinal Products for Human Use (CHMP). Recruitment of subjects into this study was challenging, and following agreement with the European Medicines Agency (EMA) enrollment into this study was halted after the enrollment of 42 of the 225 planned subjects.

The primary endpoint of the study evaluated changes in expression of biomarkers associated with immunomodulation between a pre-treatment biopsy and the disease progression biopsy. Secondary efficacy endpoints included overall response rate, clinical benefit rate and progression-free survival (PFS), as well as safety/tolerability. All subjects received study treatment until disease progression, death, unacceptable toxicity, or subject withdrawal. In case of disease progression during the treatment period, the subject was followed-up for 30 days for safety evaluation. In case of study treatment discontinuation for any reasons other than disease progression, the subject was followed-up for safety and efficacy assessments until disease progression, new anticancer therapy, death, withdrawal of consent or end of study, whichever came first.

This study supported a better understanding of the rapidly accumulating evidence for the importance of the immune microenvironment in HER2-positive breast cancer and the observed immunomodulation in the neoadjuvant setting could be confirmed in the advanced setting and supported the putative mechanism of action of HER2 dual blockade and its potential function on the tumor microenvironment. No formal comparisons between treatment arms were undertaken.

Participants were randomized to Arms A and B but randomized to Arm C.

This was a two-cohort, three-arm, open-label Phase II study to evaluate the changes in the expression of biomarkers between pre-treatment and progression biopsy in subjects with Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Subjects were allocated to 1 of 2 cohorts depending on the molecular subtype of their biopsy.

Cohort 1 HER2 -enriched included HER2-positive subjects with a HER2-Enriched molecular subtype, and were randomized in a 1:1 ratio to receive either trastuzumab in combination with lapatinib (Arm A) or trastuzumab in combination with chemotherapy (Arm B).

Cohort 2 non-HER2-enriched, included HER2-positive subjects with luminal A, luminal B, and basal-like molecular subtypes and were to receive trastuzumab in combination with lapatinib (Arm C). Subjects with hormone receptor (ER and/or PgR)-positive MBC in this arm were required to be treated with an AI of the Investigator's choice.

Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer

An Open-Label, Phase II, Study to Evaluate Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer Receiving Treatment With Trastuzumab in Combination With Lapatinib or Chemotherapy (EGF117165)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Evaluate changes in biomarkers associated with immunomodulation between pre-treatment biopsy and disease progression biopsy within each arm. Biomarker analysis was performed using an mRNA gene expression panel derived from Nanostring platform in a total of 20 subjects who received the study treatment as per the study design and with baseline tumor biopsies available.

For the selected biomarkers associated with immunomodulation, the median fold changes of gene expression level and 95% confidence interval are presented. The fold change was calculated as the ratio of the expression level of a biomarker at disease progression over the baseline.

PFS was defined as the time from the date of randomization (for Arm A and B) / treatment start date (for Arm C) to the date of the first documented disease progression or death due to any cause, whichever was earlier. If a subject had not progressed or died at the analysis cutoff date, PFS was censored at the time of the last adequate tumor assessment. PFS was summarized using Kaplan-Meier estimates.

Overall response rate was defined as the percentage of subjects achieving either a confirmed complete response (CR) or partial response (PR) and was calculated from the Investigator's assessment of response per RECIST 1.1 criteria. . The confirmed CR or PR was derived using the following rules: confirmed CR - at least two determinations of CR at least 4 weeks apart before disease progression; confirmed PR - at least two determinations of PR or better at least 4 weeks apart before progression.

CBR is defined as percentage of subjects with a complete response (CR), partial response (PR), or maintaining stable disease (SD) for at least 24 weeks while on study according to the investigator assessment of response per RECIST 1.1 criteria. CR and PR are confirmed responses derived using the following rules: Confirmed CR - at least 2 determinations of CR at least 4 weeks apart before disease progression. Confirmed PR - at least 2 determinations of PR or better at least 4 weeks apart before progression.

Describe if changes of biomarker expression at disease progression from baseline correlate with PFS.

Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.

Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

LAP+TRAS±AI (HER2-Enriched) - Arm A

Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.

TRAS+CHEM±AI (HER2-Enriched) • ArmB

Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

Non-HER2-Enriched - Arm C

TRAS+CHEM±AI (HER2-Enriched) - Arm B

Non-HER2- Enriched - Arm C

Total

< 65 years

>= 65 years

Age, Customized

Sex: Female, Male

Caucasian

African American

Asian

Native Hawaiian or Pacific Islander

Race/Ethnicity, Customized

Full Analysis Set (FAS): Consisted of all subjects who were randomized to study Arm A or Arm B or assigned to study Arm C, irrespective of whether they actually received study treatment.

Study Director

Membrane spanning 4-domains A1

POU class 2 associating factor 1

CD19+

Interleukin 6

G antigen 1

ubiquitin specific peptidase 9, Y-linked

Thy-1 cell surface antigen

Chemerin chemokine-like receptor 1

Major histocompatibility complex, class II, DR beta 4

Collectin subfamily member 12

Complement C3b/C4b receptor 1 (Knops blood group)

CD33 molecule

B-cell linker

Interleukin 12A

CD163+

C-C motif chemokine ligand 8

Chemokine (C-C motif) receptor 1

POU class 2 homeobox 2

Cyclin dependent kinase inhibitor 1A

CD27 molecule

Lymphocyte antigen 86

TNF superfamily member 8

CD34+

Integrin subunit alpha 6

C-type lectin domain containing 7A

CD180 molecule

Integrin subunit alpha M

Toll like receptor 6

Autophagy related 10

C-C motif chemokine ligand 3 like 1

Bone marrow stromal cell antigen 1

CD22+

CD37 molecule

NEG_A

Sperm auto antigenic protein 17

CD200 molecule

TNF receptor associated factor 3

Interferon alpha and beta receptor subunit 1

TNF receptor associated factor 6

Evaluable Set: Included all subjects in Arm A who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years

C-type lectin domain containing 5A

Interferon induced transmembrane protein 1

Fibronectin 1

C-C motif chemokine ligand 7

Triggering receptor expressed on myeloid cells 1

Plasminogen activator, urokinase

Interleukin 22 receptor subunit alpha 2

Tumor necrosis factor (ligand) superfamily member 4 gene

Major histocompatibility complex, Class I-related

Cathepsin L

SPP-1 (Osteopontin)

Transforming growth factor beta 2

Hepatitis A virus cellular receptor 2

C-X-C motif chemokine ligand 5

Collagen type III alpha 1 chain

Complement C1s

IFIT1 gene

Major histocompatibility complex, class I, G

Tumour necrosis factor gene

Integrin subunit beta 1

Pro-melanin concentrating hormone

CD86+

FCGR3A SNP rs396991

TNF receptor superfamily member 10c

TNF receptor superfamily member 11b

Platelet derived growth factor C

Mannan binding lectin serine peptidase 1

Recombination activating 1

Interleukin 22

Tumor necrosis factor (ligand) superfamily member 13b gene

BMI1 proto-oncogene, polycomb ring finger

CXCL10 gene

Leukocyte immunoglobulin like receptor B1

MX1 gene

Tumor necrosis factor (ligand) superfamily member 11 gene

Cathepsin S

Interferon induced transmembrane protein 2

LYN proto-oncogene, Src family tyrosine kinase

Platelet derived growth factor receptor beta

OAS3 gene

CD58 molecule

complement C3a receptor 1

Interleukin 24 gene

Chemokine (C-X-C motif) receptor 2

Strawberry notch homolog 2

Zinc finger protein 205

Fas associated via death domain

CD3e molecule associated protein

Baculoviral IAP repeat containing 5

Interleukin 17 receptor B

Evaluable Set: Included all subjects in Arm B who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years

Interleukin 1 receptor, type 1 gene

Complement component 2

Coagulation factor XII

Evaluable Set: Included all subjects in Arm C who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Fold Change in Expression Profile of Genes and /or Proteins for Arm C (Non-HER2- Enriched) From Screening to Approx. 3.5 Years

Progression-free Survival (PFS)

Overall Response Rate (ORR)

Clinical Benefit Rate (CBR)

The number of patients with available biomarker data at both baseline and at progression is very small within each treatment arm (Arm A: n=7, Arm B: n=5, Arm C: n=5). This number of subjects is insufficient for an analysis to establish a relationship between the changes in biomarker at disease progression and progression free survival and would be statistically inappropriate to fit a model correlating changes in biomarkers with progression free survival with so few patients.

Association Between Biomarkers and PFS

Total Deaths

On-treatment deaths

On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for Lapatinib, (treatment duration ranged from 151 to 164 weeks), 164 weeks for Trastuzumab (treatment duration ranged from 0 to 160 weeks), 168 weeks for Aromatase Inhibitors (treatment duration ranged from 9 to 164 weeks).

Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 5.6 years.

Clinical Database Population: All treated participants.

All-Collected Deaths

Overall Study

Spots Global Cancer Trial Database for prosigna

Every month we try and update this database with for prosigna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Observational Study Evaluating Treatment Decision Impact of Prosigna® in Early Stage Breast Cancer Patients	NCT02625935	Breast Cancer		-	NanoString Technologies, Inc.
A Prospective Observational Study of Clinical Outcomes for the NanoString® Technologies Prosigna Gene Signature Assay	NCT01899079	Breast Cancer		-	NanoString Technologies, Inc.
Prospective Observational Study Evaluating Treatment Decision Impact of Prosigna® in Early Stage Breast Cancer Patients	NCT02625935	Breast Cancer		-	NanoString Technologies, Inc.
Prospective Observational Study Evaluating Treatment Decision Impact of Prosigna® in Early Stage Breast Cancer Patients	NCT02625935	Breast Cancer		-	NanoString Technologies, Inc.
Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer	NCT02213042	Neoplasms, Brea...	Lapatinib Trastuzumab Aromatase Inhib...	18 Years -	Novartis
A Prospective Observational Study of Clinical Outcomes for the NanoString® Technologies Prosigna Gene Signature Assay	NCT01899079	Breast Cancer		-	NanoString Technologies, Inc.

Spots Global Cancer Trial Database for prosigna

Every month we try and update this database with for prosigna cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for prosigna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.