Biomarker Research Study for PF-03084014 in cHEmoresistant triple negative breast cAncer - RHEA” study

Phase 1

• Conditions: MedDRA version: 17.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; patients with chemoresistant, triple-negative breast cancer

• Registration Number: EUCTR2014-004358-32-BE
• Lead Sponsor: Institut Jules Bordet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-03-19
• Last Update Posted: 10 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 35

Inclusion Criteria

1.Age =18 years old.
2.Female.
3.Histological diagnosis of breast adenocarcinoma that is estrogen receptor-negative, progesterone receptor-negative and HER2-negative as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines (1) (triple negative).
Patients with inflammatory breast cancer are eligible.
Patients with synchronous bilateral cancer and unilateral multifocal or multicentric disease will be allowed to enter the study as long as:
•Histologic diagnosis of triple-negative breast adenocarcinoma is found in both breast tumor biopsies in case of synchronous bilateral disease.
•Histologic diagnosis of triple-negative breast adenocarcinoma can be found in all tumor foci biopsies either in same or different breast quadrants in the case of multifocal and multicentric disease, respectively. Biopsy of all tumor foci at diagnosis is not required for study eligibility.

4.No clinical or radiologic evidence of distant metastasis.

5.Residual tumor breast adenocarcinoma of at least 1.5 cm (largest focus for bilateral, multifocal or multicentric disease) as assessed by breast magnetic resonance imaging (MRI) or ultrasound (US), performed within 14 days prior to or on the day of the neoadjuvant chemotherapy administration.
6.Completion of standard anthracycline and taxane-based neoadjuvant chemotherapy. The use of platinum agents in combination with standard neoadjuvant chemotherapy is allowed. The screening schedule is based on the last chemotherapy regimen, and is as follows:
•for patients receiving taxanes every 3 weeks or taxanes in combination with a platinum agent: the screening period is at least 21 days but no later than 27 days after the day of last chemotherapy administration;
•for patients receiving weekly taxanes: the screening period is at least 7 days but no later than 13 days after the day of last chemotherapy administration.

7.ECOG Performance Status (PS) 0 or 1 assessed within 6 days of first PF-03084014 administration.
8.Adequate Bone Marrow Function to be assessed within 6 days of first PF-03084014 administration, including:
a.Absolute Neutrophil Count (ANC) =1500/µL or =1.5 x 109/L;
b.Platelets =100000/µL or =100 x 109/L;
c.Hemoglobin = 9 g/dL.
9.Adequate Renal Function to be assessed within 6 days of first PF-03084014 administration, including: Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated creatinine clearance = 60 ml/min as calculated using the method standard for the institution.
10.Adequate Liver Function to be assessed within 6 days of first PF-03084014 administration, including all of the following parameters:
a.Total serum bilirubin = 1.0 x ULN ; in case of known Gilberts syndrome a total bilirubin of up to 2 x ULN is permitted.
b.Aspartate and Alanine Aminotransferase (AST and ALT) = 1.5 x ULN;
c.Alkaline phosphatase = 2.5 x ULN.
11.Serum/urine pregnancy test (for patients of childbearing potential) negative within 6 days prior to first PF-03084014.
12.Patients of childbearing potential (i.e. not permanently sterilized or not meeting criteria for postmenopausal status) must agree to the use of two (2) methods of highly effective contraception while receiving treatment with PF-03084014 and continued for at least 90 days after the last dose (including non-hormonal (copper-containing) intrauterine device, condom with spermicidal foam/gel/film/cream/suppository, occlusive cap (diaphragm or cervical/vault caps) wit

Exclusion Criteria

1.Concurrent treatment with chemotherapy, hormone replacement therapy, oral contraceptives, radiotherapy, bisphosphonates (either in oral, subcutaneous and intravenous administration forms), Denosumab, and any investigational therapy under evaluation in another clinical study, during the time of PF-03084014 administration.
2.Pregnant or lactating women.
3.Any prior history of invasive breast cancer.
4.Any history of non-breast malignancies within the 5 years preceding study entry except for basal cell and squamous cell carcinomas of the skin or any ongoing non-breast malignancy diagnosed more than 5 years ago.
5.Known hypersensitivity to the study drug or excipients.
6.Any illness or medical condition that is unstable or could jeopardize the safety of the patient or her compliance with study requirements.
7.Evidence of any residual grade 2 or worse toxicity (with the exception of alopecia) related to chemotherapy.
8.Subjects unable to swallow oral medications.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that a 9-day administration of oral PF-03084014 is able to modulate the Notch pathway by down-regulating the expression of the tumor HES4 gene in chemoresistant TNBC (evaluable population for the primary objective).;Secondary Objective: 1.To determine if a short administration of oral PF-03084014 is safe in patients with chemoresistant TNBC ( safety population) <br>2.To assess changes in the tumor transcriptome before and after short administration of oral PF-03084014 (evaluable population for the secondary objective of transcriptome analysis )<br>;Primary end point(s): Tumor HES4 gene expression will be evaluated using reverse transcription polymerase chain reaction (RT-PCR) at the end of the study) from FFPE tumor tissue collected before and after PF-03084014 administration period. ;Timepoint(s) of evaluation of this end point: at the end of the study from FFPE tumor tissue collected before and after PF-03084014 administration period.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Complete tumor transcriptome will be evaluated using RNA sequencing on frozen tumor tissue collected before and after administration of PF-03084014.;Timepoint(s) of evaluation of this end point: at the end of the study.