NCT02101385

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

A Phase II Randomized Controlled Trial of Genomically Directed Therapy After Preoperative Chemotherapy in Patients With Triple Negative Breast Cancer: Hoosier Oncology Group BRE12-158

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 193 (actual)
• Sponsor: Bryan Schneider, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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 description

OUTLINE: This is a multi-center trial. SEQUENCING: 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. CANCER GENOMICS TUMOR BOARD (CGTB): 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 TREATMENT RECOMMENDATION: Participants with a CGTB recommendation will be randomized to Experimental Arm A (genomically directed monotherapy) or Control Arm B (standard therapy). EXPERIMENTAL ARM A (GENOMICALLY DIRECTED MONOTHERAPY): 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. TOP GENOMIC ACTIONABLE BIOMARKERS/PATHWAYS AND DRUG RECOMMENDATIONS: 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 WITH NO CGTB RECOMMENDATION: 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: Hematopoietic: * Hemoglobin (Hgb) ≥ 9.0 g/dL * Platelets ≥ 100 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 Hepatic: * 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 Renal: * Calculated creatinine clearance of ≥ 50 cc/min using the Cockcroft-Gault formula Cardiac: * 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

Conditions

• Malignant Neoplasm of Breast
• Breast Cancer

Interventions

Type	Name	Description
DRUG	Genomically Directed Monotherapy	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). The CGTB will assign therapy to each participant individually based on biomarkers/pathways identified by DNA sequencing:
OTHER	Observation/Standard Therapy	Currently no standard therapy has proven efficacy in this patient population and thus observation alone would be considered standard of care. Additional therapy is permitted, however, if deemed appropriate by the treating physician.

Timeline

• Start date: 2014-04-03
• Primary completion: 2021-02-21
• Completion: 2022-09-09
• First posted: 2014-04-02
• Last updated: 2023-09-28
• Results posted: 2023-09-28

Locations

29 sites across 1 country: United States