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

Breast Cancer Clinical Trial

— RHEA  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02338531
• Other study ID #: IJB-TNBC-1-RHEA
• Secondary ID: 2014-004358-32
• Status: Withdrawn
• Phase: Phase 2
• First received: January 5, 2015
• Last updated: April 28, 2016
• Start date: June 2015
• Est. completion date: December 2018

Study information

• Verified date: April 2016
• Source: Jules Bordet Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPFrance: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years old.

2. Female.

3. 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).

4. No clinical or radiologic evidence of distant metastasis.

5. 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.

6. Completion of standard anthracycline and taxane-based neoadjuvant chemotherapy. The use of platinum agents in combination with standard neoadjuvant chemotherapy is allowed.

7. ECOG Performance Status (PS) 0 or 1

8. 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.

9. Adequate Renal Function: Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated creatinine clearance = 60 ml/min.

10. 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.

11. 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:

1. Concurrent anti-cancer therapy for current breast cancer (hormone therapy, chemotherapy, radiotherapy, immunotherapy). Patients already included in another therapeutic trial involving an experimental drug.

2. Pregnant or lactating women.

3. Any prior history of invasive breast cancer.

4. Any previous history of non-breast malignancies (excepted basal cell carcinoma or squamous cell carcinoma of the skin) in the preceding 5 years.

5. Known hypersensitivity to the study drug or excipients.

6. Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study.

7. Subjects unable to swallow oral medications.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• PF-03084014

Procedure:
• Breast cancer surgery

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	CMSE	Namur
France	Institut Curie	Paris
France	Institut de Cancérologie Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Jules Bordet Institute

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	tumour tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.	No
Secondary	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.	adverse events followed up to 28 days after last PF-03084014 dose.	Yes
Secondary	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)	tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.	No