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Thero2-01S22 in HER2-positive Breast Cancer

Primary Purpose

HER2-positive Breast Cancer

Status

Not yet recruiting

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Thero2-01S22

Placebo

Thero2-01S22

Placebo

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Women aged > 18 Metastatic setting of an histologically confirmed adenocarcinoma of the breast Performance status = 0, 1 or 2 Metastatic disease requiring the initiation of an anti HER2 containing regimen First line treatment for metastatic disease Standard treatment including Trastuzumab and Pertuzumab in first line Patients for whom a 3-month life expectancy is anticipated Baseline LVEF value > 50%, measured cardiac MRI or by echocardiography (Simpson's method) or MUGA scan within 12 weeks before initiation of the treatment. According to HERCEPTIN SPCs. Overexpression of HER2 in the invasive component of the primary tumor (3+ by ICH or 2+ with confirmation of positivity by FISH or CISH) Informed consent form signed Exclusion Criteria: Patients not eligible for anti-HER2 therapy Patients previously treated at the metastatic setting by systemic treatment Serious cardiac illness or medical conditions disallowing administration of anti-HER2 therapy. According to HERCEPTIN and PERJETA SPCs. Known hypersensitivity to trastuzumab, pertuzumab, Thero2-01S22, murine proteins or to any of the excipients. Uncontrolled central nervous system metastatic lesion Patients who, for social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls Pregnant or breastfeeding women

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

Part 1: Anti-HER2 targeted therapy containing regimen + Placebo

Part 2: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

Part 2: Anti-HER2 targeted therapy containing regimen + Placebo

Arm Description

Patients will receive Thero2-01S22 at the recommended dose and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Patients will receive placebo and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Patients will receive Thero2-01S22 at the confirmed dose and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Outcomes

Primary Outcome Measures

Part 1: confirm the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast for Part 2

Incidence of adverse events considered possibly related to Thero2-01S22 that occur any time from the first dose intake of IMP or placebo to week 6.

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Objective response rate (ORR) at week 6

Objective response rate (ORR): Percentage of patients whose disease decreased (Partial Response, PR) and / or disappears (Complete Response, CR) after treatment, according to RECIST V1.1 criteria, Eisenhauer et al. 2009.

Secondary Outcome Measures

Part 1: determine the safety of the recommended dose of Thero2-01S22as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

Safety: Incidence of adverse events per Common Terminology Criteria for Adverse Events (graded according to CTCAE) version 5.0 criteria from randomization to week 6

Part 1: determine the tolerability of the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer in terms of dose interruption

Number of dose interruptions of Thero2-01S22 trastuzumab, pertuzumab, and induction chemotherapy. Assessment period: from randomization to week 6

Palatability of oral Thero2-01S22 measured with visual analog scale. Assessment period: from randomization to week 6

Treatment duration (number of days) of therapy including Thero2-01S22 trastuzumab, pertuzumab, and induction chemotherapy. Assessment period: from randomization to week 6

Part 1: characterize exposure of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast

Determination of Area Under Curve (AUC) after oral Thero2-01S22 administration. PK samples to be collected at day 1 of cycle 1 and cycle 2 (each cycle is 21 days): before IMP or placebo intake, and at 5, 10, 15, 60, 120, 160 minutes after the intake

Part 1: characterize exposure of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast

Determination of Maximum Plasma Concentration (Cmax) after oral Thero2-01S22 administration. PK samples to be collected at day 1 of cycle 1 and cycle 2 (each cycle is 21 days): before IMP or placebo intake, and at 5, 10, 15, 60, 120, 160 minutes after the intake

Part 1: evaluate preliminary efficacy of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Progression-Free Survival (PFS)

Progression-Free Survival (PFS): defined as the time interval from the date of randomization to the date of progression. Events considered as progression include local or distant progression, appearance of a second cancer or death (all causes) whichever occurs first

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Overall Survival (OS)

Overall Survival (OS): defined as the time interval from the date of randomization to the date of death, regardless of disease progression

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of safety

Compare the effects of anti-HER2 targeted containing regimen with and without Safety: Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs) classified according to the CTCAE v5.0 criteria

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of cardiotoxicity in terms of decrease of Left Ventricular Ejection Fraction (LVEF)

Decrease in Left Ventricular Ejection Fraction (LVEF) value compared to baseline according to the modality performed (ECG, MUGA, MRI)

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of cardiotoxicity in terms of cardiac toxicities revealed at physical examination

Cardiac toxicities revealed at physical examination, graded according to CTCAE v5.0 criteria

Full Information

NCT ID

NCT05698186

First Posted

November 30, 2022

Last Updated

January 13, 2023

Sponsor

Institut de cancérologie Strasbourg Europe

1. Study Identification

Unique Protocol Identification Number

NCT05698186

Brief Title

Thero2-01S22 in HER2-positive Breast Cancer

Official Title

A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase III Efficacy and Safety Study of Thero2-01S22 add-on Therapy on Top of First-line Anti-HER2 Targeted Treatment of Patients With Metastatic Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

May 15, 2023 (Anticipated)

Primary Completion Date

May 15, 2027 (Anticipated)

Study Completion Date

May 15, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut de cancérologie Strasbourg Europe

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Trastuzumab and pertuzumab based regimen are the standard of care for patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC), significantly improving survival outcomes. However, an unmet medical need remain for patients with disease refractoriness and recurrence. Interestingly, HER2 over-expression is associated with upregulation of vascular endothelial growth factor (VEGF) in cancer cells in vitro and in vivo. Preclinical studies indicated that VEGF expression is positively regulated by HER2 signaling. In the clinical setting, HER2 over-expression correlated significantly with VEGF over- expression in samples from patients with breast cancer. There is, therefore, a biologic rationale for targeting both HER2 and VEGF pathways in patients with HER2-positive breast cancer. PURPOSE: The hypothesis that justifies this research is that the addition of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment will improve the efficacy of anti-HER2 targeted containing regimen at the metastatic setting for breast cancer.

Detailed Description

This study is a two-part, multicenter, randomized, double-blind, placebo-controlled, Phase III trial. Part 1 will confirm the recommended Phase III dose of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast, with the aim to obtain about 15 evaluable participants in Thero2-01S22 group and 15 in the placebo group. Part 2 will assess the efficacy of Thero2-01S22 treatment at the recommended dose when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast. Approximately 290 participants will be randomized to receive Thero2-01S22 or Thero2-01S22 matching-placebo in combination with trastuzumab and pertuzumab. Participants in both Part 1 and Part 2 will receive induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Anti-HER2 targeted therapy containing regimen + Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 2: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Anti-HER2 targeted therapy containing regimen + Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Thero2-01S22

Intervention Description

Blinded recommended dose BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Blinded placebo BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Intervention Type

Drug

Intervention Name(s)

Thero2-01S22

Intervention Description

Blinded confirmed dose BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Blinded placebo BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Primary Outcome Measure Information:

Title

Part 1: confirm the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast for Part 2

Description

Incidence of adverse events considered possibly related to Thero2-01S22 that occur any time from the first dose intake of IMP or placebo to week 6.

Time Frame

Week 6

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Objective response rate (ORR) at week 6

Description

Time Frame

Week 6

Secondary Outcome Measure Information:

Title

Part 1: determine the safety of the recommended dose of Thero2-01S22as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

Description

Safety: Incidence of adverse events per Common Terminology Criteria for Adverse Events (graded according to CTCAE) version 5.0 criteria from randomization to week 6

Time Frame

Week 6

Title

Description

Number of dose interruptions of Thero2-01S22 trastuzumab, pertuzumab, and induction chemotherapy. Assessment period: from randomization to week 6

Time Frame

Week 6

Title

Description

Palatability of oral Thero2-01S22 measured with visual analog scale. Assessment period: from randomization to week 6

Time Frame

Week 6

Title

Description

Treatment duration (number of days) of therapy including Thero2-01S22 trastuzumab, pertuzumab, and induction chemotherapy. Assessment period: from randomization to week 6

Time Frame

From randomization to Week 6

Title

Part 1: characterize exposure of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast

Description

Time Frame

PK samples at day 1 of cycle 1 and cycle 2(each cycle is 21 days): before IMP or placebo intake, and at 5, 10, 15, 60, 120, 160 minutes after the intake

Title

Part 1: characterize exposure of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast

Description

Time Frame

PK samples at day 1 of cycle 1 and cycle 2(each cycle is 21 days): before IMP or placebo intake, and at 5, 10, 15, 60, 120, 160 minutes after the intake

Title

Part 1: evaluate preliminary efficacy of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

Description

Time Frame

Week 6

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Progression-Free Survival (PFS)

Description

Time Frame

Up to 24 months

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Overall Survival (OS)

Description

Overall Survival (OS): defined as the time interval from the date of randomization to the date of death, regardless of disease progression

Time Frame

Up to 24 months

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of safety

Description

Time Frame

Week 6 and up to the end of the study (24 months)

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of cardiotoxicity in terms of decrease of Left Ventricular Ejection Fraction (LVEF)

Description

Decrease in Left Ventricular Ejection Fraction (LVEF) value compared to baseline according to the modality performed (ECG, MUGA, MRI)

Time Frame

From week 6 up to 24 months

Title

Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of cardiotoxicity in terms of cardiac toxicities revealed at physical examination

Description

Cardiac toxicities revealed at physical examination, graded according to CTCAE v5.0 criteria

Time Frame

From week 6 up to 24 months

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Valérie SARTORI

Phone

368767223

Ext

v.sartori@icans.eu

First Name & Middle Initial & Last Name or Official Title & Degree

Manon VOEGELIN

Phone

368767360

Ext

promotion-rc@icans.eu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xavier PIVOT, MD, PhD

Organizational Affiliation

Institut de cancérologie Strasbourg Europe

Official's Role

Study Chair

12. IPD Sharing Statement

Learn more about this trial

Thero2-01S22 in HER2-positive Breast Cancer

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