Clinical trial NCT02338531: Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer
Official title: Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: HES4 gene expression level
timeFrame: tumour tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.
Secondary outcomes:
measure: Safety: General assesment of number and grade of adverse events after short(9-day) administration of oral PF-03084014 in patients with chemoresistant TNBC.
timeFrame: adverse events followed up to 28 days after last PF-03084014 dose.
measure: Transcriptome analysis (changes in the HES4 gene expression and tumor transcriptome)
timeFrame: tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Namur
country: Belgium
facility: CMSE
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Institut de Cancérologie Gustave Roussy
Study officials:
affiliation: Medical Oncology Department
name: Michail Ignatiadis, MD, PhD
role: STUDY_DIRECTOR
References: