Last updated on February 2019

Randomized Controlled Trial of Genomically Directed Therapy in Patients With Triple Negative Breast Cancer

Brief description of study

This study will test the theory that therapy designed for each individual's tumor will improve outcomes over standard of care in a population that needs a better standard.

Detailed Study Description

OUTLINE: This is a multi-center trial.


DNA from archived tumor samples collected at the time of surgery (residual disease post neoadjuvant chemotherapy) will be extracted and sequenced. The resulting sequencing data will be interrogated for known genomic drivers of sensitivity or resistance to existing FDA approved agents.


Realizing that optimal treatment recommendations cannot be made based on sequencing data alone, the CGTB will be responsible for the final treatment recommendation. The CGTB will consider the genomic data along with the patient's prior treatment history, ongoing toxicities, and comorbidities. Preference will be given to the treatment identified by the sequencing data unless a significant clinical or safety contraindication exists for that therapy. All participants and investigators will be blinded to sequencing results and CGTB deliberations until the time of relapse.


Participants with a CGTB recommendation will be randomized to Experimental Arm A (genomically directed monotherapy) or Control Arm B (standard therapy).


Participants randomized to Experimental Arm A will receive an FDA approved drug at standard dose for four cycles (12-16 weeks total duration, depending on cycle length). Clinical and laboratory monitoring and dose-reductions will follow the FDA package insert guidelines.


  1. PIK3CA, PTEN: Everolimus
  2. TOP2A: Doxorubicin
  3. PARP1, BRCA1: Cisplatin and Olaparib
  4. VEGFA: Bevacizumab
  5. TYMP: Capecitabine
  6. SSTR2: Octreotide
  7. MGMT: Temozolomide
  8. MYC: Paclitaxel
  9. EGFR: Cetuximab
  10. COX2: Celecoxib
  11. hENT: Gemcitabine
  12. MET: Crizotinib

CONTROL ARM B (STANDARD THERAPY); Recently, a randomized phase III trial of over 900 HER2-negative patients demonstrated an improvement in disease-free survival (DFS) and overall survival (OS) for the addition of 8 cycles of capecitabine in the post-neoadjuvant setting. The hazard ratios were also significant in the triple negative subgroup. Thus, capecitabine can be considered a standard option in this setting. As this represents only a single trial (with prior data not demonstrating benefit for the addition of capecitabine in the neoadjuvant nor adjuvant settings in unselected patients), observation can be considered an option as directed by the treating physician. While not recommended, other therapies can be used as deemed appropriate by the treating physician.

In the event of disease progression on the control arm, patient sequencing results will be forwarded to the treating physician.


Participants may have no CGTB recommendation either because 1) sequencing did not identify a matched drug or 2) the matched drug was contraindicated. These participants will be assigned to Control Arm B and treated as described above for Control Arm B. As the outcome of participants without an 'actionable' genomically directed therapy may differ, the primary analysis will include only participants randomized to Control Arm B.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to study registration

Life Expectancy: Not Specified

Adequate laboratory values must be obtained within 14 days prior to study registration:

  • Hemoglobin (Hgb) 9.0 g/dL
  • Platelets 100 K/mm3
  • Absolute neutrophil count (ANC) 1.5 K/mm3
  • Bilirubin 1.5 x ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin 3.0 mg/dL)
  • Aspartate aminotransferase (AST, SGOT) 2.5 x ULN
  • Alanine aminotransferase (ALT, SGPT) 2.5 x ULN
  • Calculated creatinine clearance of 50 cc/min using the Cockcroft-Gault formula
  • Left ventricular ejection fraction within normal limits obtained within 30 days prior to study registration. NOTE: Participants with an unstable angina or myocardial infarction within 12 months of study registration are excluded.
  • No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating physician

Clinical Study Identifier: NCT02101385

Contact Investigators or Research Sites near you

Start Over

IU Health Goshen Hospital

Goshen, IN United States

Recruitment Status: Closed

Brief Description Eligibility Contact Research Team

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