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Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer (RHEA)

Primary Purpose

Breast Cancer

Status

Withdrawn

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

PF-03084014

Breast cancer surgery

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

Age ≥18 years old.
Female.
Histological diagnosis of triple-negative breast cancer (TNBC) breast adenocarcinoma (ER<1%, PR<1% by (IHC) and HER-2 0-1+ by IHC or IHC 2+ and FISH or CISH negative per updated ASCO guidelines).
No clinical or radiologic evidence of distant metastasis.
Presence of residual primary disease of at least 1.5 cm by U/S or MRI within 14 days preceding the last cycle of standard anthracycline and taxane-based neoadjuvant chemotherapy.
Patients with synchronous synchronous bilateral cancer and unilateral multifocal or multicentric or bilateral disease breast cancer will be allowed provided histologic diagnosis of TNBC is found on all performed biopsies.
Completion of standard anthracycline and taxane-based neoadjuvant chemotherapy. The use of platinum agents in combination with standard neoadjuvant chemotherapy is allowed.
ECOG Performance Status (PS) 0 or 1
Adequate Bone Marrow Function: Absolute Neutrophil Count (ANC) ≥ 1500/μL or ≥1.5 x 109/L; Platelets ≥100000/μL or ≥100 x 109/L; Hemoglobin ≥ 9 g/dL.
Adequate Renal Function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min.
Adequate Liver Function:Total serum bilirubin ≤ 1.0 x ULN or ≤ 2 x ULN in cases of known Gilberts syndrome; Aspartate and Alanine Aminotransferase (AST and ALT) ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN.
For patients of childbearing potential: negative serum/urine pregnancy test and use accepted forms of non-hormonal contraception during the study period and up to 6 months after treatment completion.

Exclusion Criteria:

Concurrent anti-cancer therapy for current breast cancer (hormone therapy, chemotherapy, radiotherapy, immunotherapy). Patients already included in another therapeutic trial involving an experimental drug.
Pregnant or lactating women.
Any prior history of invasive breast cancer.
Any previous history of non-breast malignancies (excepted basal cell carcinoma or squamous cell carcinoma of the skin) in the preceding 5 years.
Known hypersensitivity to the study drug or excipients.
Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study.
Subjects unable to swallow oral medications.

Sites / Locations

Institut Jules Bordet
Grand Hopital de Charleroi
CMSE
Institut Curie
Institut de Cancérologie Gustave Roussy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic regimen

Arm Description

oral administration of PF-03084014, 9 days at 150 mg q.d. (day 1 and 9) and 150 b.i.d. (day 2 till 8)

Outcomes

Primary Outcome Measures

HES4 gene expression level

To demonstrate that PF-03084014 is able to modulate the Notch pathway by down-regulating the expression of the tumor HES4 gene in chemoresistant TNBC (evaluable population).

Secondary Outcome Measures

Safety: General assesment of number and grade of adverse events after short(9-day) administration of oral PF-03084014 in patients with chemoresistant TNBC.

Patients will be followed for Adverse Events and Serious Adverse Events from the first dose of study drug up to 28 days after the last dose.

Transcriptome analysis (changes in the HES4 gene expression and tumor transcriptome)

To assess changes in the HES4 gene expression and tumor transcriptome for all patients registered in the RHEA study (intent-to-treat population)

Full Information

NCT ID

NCT02338531

First Posted

January 5, 2015

Last Updated

April 28, 2016

Sponsor

Jules Bordet Institute

1. Study Identification

Unique Protocol Identification Number

NCT02338531

Brief Title

Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer

Acronym

RHEA

Official Title

Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Withdrawn

Why Stopped

Due to the discontinuation of the development of the Notch inhibitor PF-03084014-04

Study Start Date

June 2015 (undefined)

Primary Completion Date

September 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jules Bordet Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a phase II open label Biomarker Research Study off PF-03084014 in non-metastatic triple-negative breast cancer patients with residual disease (cHEmoresistant) after completion of standard neoadjuvant chemotherapy.

6. Conditions and Keywords

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

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Therapeutic regimen

Arm Type

Experimental

Arm Description

oral administration of PF-03084014, 9 days at 150 mg q.d. (day 1 and 9) and 150 b.i.d. (day 2 till 8)

Intervention Type

Drug

Intervention Name(s)

PF-03084014

Intervention Type

Procedure

Intervention Name(s)

Breast cancer surgery

Primary Outcome Measure Information:

Title

HES4 gene expression level

Description

To demonstrate that PF-03084014 is able to modulate the Notch pathway by down-regulating the expression of the tumor HES4 gene in chemoresistant TNBC (evaluable population).

Time Frame

tumour tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.

Secondary Outcome Measure Information:

Title

Safety: General assesment of number and grade of adverse events after short(9-day) administration of oral PF-03084014 in patients with chemoresistant TNBC.

Description

Patients will be followed for Adverse Events and Serious Adverse Events from the first dose of study drug up to 28 days after the last dose.

Time Frame

adverse events followed up to 28 days after last PF-03084014 dose.

Title

Transcriptome analysis (changes in the HES4 gene expression and tumor transcriptome)

Description

To assess changes in the HES4 gene expression and tumor transcriptome for all patients registered in the RHEA study (intent-to-treat population)

Time Frame

tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥18 years old. Female. Histological diagnosis of triple-negative breast cancer (TNBC) breast adenocarcinoma (ER<1%, PR<1% by (IHC) and HER-2 0-1+ by IHC or IHC 2+ and FISH or CISH negative per updated ASCO guidelines). No clinical or radiologic evidence of distant metastasis. Presence of residual primary disease of at least 1.5 cm by U/S or MRI within 14 days preceding the last cycle of standard anthracycline and taxane-based neoadjuvant chemotherapy. Patients with synchronous synchronous bilateral cancer and unilateral multifocal or multicentric or bilateral disease breast cancer will be allowed provided histologic diagnosis of TNBC is found on all performed biopsies. Completion of standard anthracycline and taxane-based neoadjuvant chemotherapy. The use of platinum agents in combination with standard neoadjuvant chemotherapy is allowed. ECOG Performance Status (PS) 0 or 1 Adequate Bone Marrow Function: Absolute Neutrophil Count (ANC) ≥ 1500/μL or ≥1.5 x 109/L; Platelets ≥100000/μL or ≥100 x 109/L; Hemoglobin ≥ 9 g/dL. Adequate Renal Function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min. Adequate Liver Function:Total serum bilirubin ≤ 1.0 x ULN or ≤ 2 x ULN in cases of known Gilberts syndrome; Aspartate and Alanine Aminotransferase (AST and ALT) ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN. For patients of childbearing potential: negative serum/urine pregnancy test and use accepted forms of non-hormonal contraception during the study period and up to 6 months after treatment completion. Exclusion Criteria: Concurrent anti-cancer therapy for current breast cancer (hormone therapy, chemotherapy, radiotherapy, immunotherapy). Patients already included in another therapeutic trial involving an experimental drug. Pregnant or lactating women. Any prior history of invasive breast cancer. Any previous history of non-breast malignancies (excepted basal cell carcinoma or squamous cell carcinoma of the skin) in the preceding 5 years. Known hypersensitivity to the study drug or excipients. Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study. Subjects unable to swallow oral medications.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michail Ignatiadis, MD, PhD

Organizational Affiliation

Medical Oncology Department

Official's Role

Study Director

Facility Information:

Facility Name

Institut Jules Bordet

City

Brussels

ZIP/Postal Code

1000

Country

Belgium

Facility Name

Grand Hopital de Charleroi

City

Charleroi

ZIP/Postal Code

6000

Country

Belgium

Facility Name

CMSE

City

Namur

ZIP/Postal Code

5000

Country

Belgium

Facility Name

Institut Curie

City

Paris

ZIP/Postal Code

750005

Country

France

Facility Name

Institut de Cancérologie Gustave Roussy

City

Villejuif

ZIP/Postal Code

94800

Country

France

12. IPD Sharing Statement

Learn more about this trial

Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer

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