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

NCT02338531 | Withdrawn Phase 2

• 2 other identifiers: IJB-TNBC-1-RHEA2014-004358-32
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 5

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (2)

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

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

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

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

Study Arms (1)

Therapeutic regimen

EXPERIMENTAL

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)

Drug: PF-03084014; Procedure: Breast cancer surgery

Interventions

PF-03084014 DRUG

Therapeutic regimen

Breast cancer surgery PROCEDURE

Therapeutic regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (5)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

CMSE

Namur, 5000, Belgium

Location

Institut Curie

Paris, 750005, France

Location

Institut de Cancérologie Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

nirogacestat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michail Ignatiadis, MD, PhD

  Medical Oncology Department

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 14, 2015
• Study Start: June 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2018
• Last Updated: April 29, 2016

Record last verified: 2016-04

Locations

BE (3); FR (2)