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

• Sponsor: Jules Bordet Institute (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT02338531
• Collaborator: (none)
• Enrollment: 0
• Locations: 5
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: PF-03084014; Procedure: Breast cancer surgery	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biomarker Research Study for PF-03084014 in cHEmoresistant Triple-negative Breast cAncer
• Study Start Date: Jun 1, 2015
• Anticipated Primary Completion Date: Sep 1, 2018
• Anticipated Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Therapeutic regimen 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

Outcome Measures

Primary Outcome Measures

1. HES4 gene expression level [tumour tissue samples before study drug and after 9 days of study drug. General analysis after all patients included.]

   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

1. 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.]

   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.

2. 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.]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

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

2. ECOG Performance Status (PS) 0 or 1

3. 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.

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

5. 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.

6. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Jules Bordet	Brussels		Belgium	1000
2	Grand Hopital de Charleroi	Charleroi		Belgium	6000
3	CMSE	Namur		Belgium	5000
4	Institut Curie	Paris		France	750005
5	Institut de Cancérologie Gustave Roussy	Villejuif		France	94800

Sponsors and Collaborators

• Jules Bordet Institute

Investigators

• Study Director: Michail Ignatiadis, MD, PhD, Medical Oncology Department

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jules Bordet Institute
• ClinicalTrials.gov Identifier: NCT02338531
• Other Study ID Numbers: IJB-TNBC-1-RHEA; 2014-004358-32
• First Posted: Jan 14, 2015
• Last Update Posted: Apr 29, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms

Study Results

No Results Posted as of Apr 29, 2016